| [effects of 10-hydroxycamptothecin on induced chromosome aberrations in chinese hamster ovary cells and micronuclei in mouse bone marrow and fetal liver]. | 10-hydroxycamptothecin (hc) is a new antitumor principle isolated from camptotheca acuminata indigenous to china. the genetic toxicity of hc was assessed by mouse bone marrow and transplacental micronucleus test as well as chinese hamster ovary cell chromosomal aberrations. all of these tests showed positive results. the highest rate of chromosomal aberrations was 83% at 0.125 microgram/ml for 48 h. the number of micronucleated polychromatic erythrocytes in bone marrow of mice was remarkably inc ... | 1990 | 2104494 |
| dna topoisomerase i as a site of action for 10-hydroxycamptothecin in human promyelocytic leukemia cells. | we investigated the antiproliferative effect of 10-hydroxycamptothecin (hcpt), an alkaloid isolated from camptotheca acuminata, on the human promyelocytic leukemia cell line, hl-60, and a 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-amsa)-resistant mutant, hl-60/m-amsa. using trypan blue dye exclusion and colony formation, doses of hcpt ranging from 0.01 to 1 microm progressively inhibited growth in both cell lines in a concentration-dependent manner. a minimal cross-resistance, approximate ... | 1990 | 2159843 |
| tannins of cornaceous plants. i. cornusiins a, b and c, dimeric monomeric and trimeric hydrolyzable tannins from cornus officinalis, and orientation of valoneoyl group in related tannins. | cornusiin a (1), cornusiin b (2) and cornusiin c (3), new dimeric, monomeric and trimeric hydrolyzable tannins, were isolated from the fruits of cornus officinalis (cornaceae). their structures, including the orientation of the valoneoyl group in 1 and 3, were established on the basis of chemical and spectroscopic data. 2,3-di-o-galloyl-d-glucose (7), 1,2,3-tri-o-galloyl-beta-d-glucose, 1,2,6-tri-o-galloyl-beta-d-glucose, 1,2,3,6-tetra-o-galloyl-beta-d-glucose, gemin d (5), isoterchebin, tellima ... | 1989 | 2480850 |
| characterization of a mammalian mutant with a camptothecin-resistant dna topoisomerase i. | dna topoisomerase i was purified to near homogeneity from a clonal line of human lymphoblastic leukemia cells, rpmi 8402, that is resistant to camptothecin, a cytotoxic alkaloid from camptotheca acuminata, and compared with that of the parent wild-type cells. as assayed by relaxation of the supercoiled plasmid dna and by formation of enzyme-linked dna breaks, the purified enzyme from the resistant cells was shown to be greater than 125-fold as resistant to camptothecin as the wild-type enzyme, c ... | 1987 | 3039492 |
| plant antitumor agents. 22. isolation of 11-hydroxycamptothecin from camptotheca acuminata decne: total synthesis and biological activity. | the antitumor alkaloid 11-hydroxy-(20s)-camptothecin was isolated from the woody tissue of camptotheca acuminata. structural proof derived from comparison with racemic 4 prepared by total synthesis. antitumor activity of racemic 4 in l1210 leukemia in mice was considerably greater than that of natural (20s)-camptothecin and its sodium salt. there was also no toxic effect observed even at relatively high doses. | 1986 | 3735324 |
| the effect of hydroxycamptothecin in the activity of rna and dna polymerases prepared from murine hepatoma cells. | hydroxycamptothecin (hcpt) is an antitumor alkaloid isolated from camptotheca acuminata indigenous to china. it could reduce the activity of nuclear rna polymerase ii and i(iii) of hepatoma cells. hcpt at 25-100 microm caused a remarkable inhibition on dna polymerase alpha whilst only a slight inhibition on beta. the inhibitory action on alpha was restored by increasing amounts of enzyme or dna template, but unchanged by varying amounts of substrate. it is suggested that hcpt may exert a stronge ... | 1985 | 4025212 |
| medicinal plants--old and new. | the historic role of plants in healing declined early in the twentieth century with the ascendency of synthetic drugs, even though a number of basic medical tools, such as opium, strychnine, and cocaine, are of botanical origin. in recent years, interest in natural products has been restored dramatically by the discovery of penicillin, plant-derived tranquilizers, and plant precursors of cortisone. contrary to previous beliefs, botanical drugs are proving more economical than synthetics and hold ... | 1968 | 5644801 |
| camptothecin analogues in the treatment of non-small cell lung cancer. | camptothecin is a natural product derived from the oriental tree camptotheca acuminata which has shown activity in a number of experimental tumors. its clinical development was halted in the early-70s owing to its unpredictable and formidable toxicities. two water-soluble camptothecin analogs have been synthesized recently and are currently in clinical trials: topotecan and cpt-11. camptothecin and its derivatives are unique in that they represent the only family of topoisomerase i inhibitors. t ... | 1995 | 7551927 |
| interaction of an alkylating camptothecin derivative with a dna base at topoisomerase i-dna cleavage sites. | dna topoisomerase i (top1) is a ubiquitous nuclear enzyme. it is specifically inhibited by camptothecin, a natural product derived from the bark of the tree camptotheca acuminata. camptothecin and several of its derivatives are presently in clinical trial and exhibit remarkable anticancer activity. the present study is a further investigation of the molecular interactions between the drug and the enzyme-dna complex. we utilized an alkylating camptothecin derivative, 7-chloromethyl-10,11-methylen ... | 1995 | 7568032 |
| sites of accumulation of the antitumor alkaloid camptothecin in camptotheca acuminata. | camptothecin is an anticancer and anti-viral alkaloid produced by the chinese tree camptotheca acuminata (nyssaceae). despite previous reports of low levels of anticancer activity in leaves of camptotheca acuminata, we have discovered that camptothecin accumulates to approximately 0.4% of the dry weight of young leaves. this level is 1.5-fold higher than that of the seeds and 2.5-fold higher than that of the bark, the two currently used sources of the drug. as the leaves mature, the concentratio ... | 1994 | 7809212 |
| camptothecin and taxol: discovery to clinic--thirteenth bruce f. cain memorial award lecture. | camptothecin and taxol are secondary metabolites found, respectively, in the wood bark of camptotheca acuminata, a native of china, and taxus brevifolia, found in the northwest pacific coastal region of the united states. the compounds were isolated guided by bioassay on various extracts and chromatographic fractions. their unique and hitherto unknown structures were elucidated by nuclear magnetic resonance, mass spectrometry, and x-ray analysis. both compounds have unique mechanisms of antitumo ... | 1995 | 7850785 |
| inhibition of phosphorylation of histone h1 and h3 induced by 10-hydroxycamptothecin, dna topoisomerase i inhibitor, in murine ascites hepatoma cells. | hydroxycamptothecin (hcpt), isolated from camptotheca acuminata, is a powerful antitumor alkaloid. previous studies indicated that the molecular target of this agent was dna topoisomerase i. the present results demonstrated that in vitro treatment of murine ascites hepatoma cells with hcpt resulted in a marked reduction in dna syntheses and the inhibition of phosphorylation in histone was in a time-dependent manner. gel electrophoresis found that hcpt had a selectively inhibitory effect on the p ... | 1993 | 8010056 |
| expression of a 3-hydroxy-3-methylglutaryl coenzyme a reductase gene from camptotheca acuminata is differentially regulated by wounding and methyl jasmonate. | we have isolated a gene, hmg1, for 3-hydroxy-3-methylglutaryl coenzyme a reductase (hmgr) from camptotheca acuminata, a chinese tree that produces the anti-cancer monoterpenoid indole alkaloid camptothecin (cpt). hmgr supplies mevalonate for the synthesis of the terpenoid component of cpt as well as for the formation of many other primary and secondary metabolites. in camptotheca, hmg1 transcripts were detected only in young seedlings and not in vegetative organs of older plants. regulation of t ... | 1993 | 8208857 |
| preclinical evaluation of cpt-11 and its active metabolite sn-38. | cpt-11 (irinotecan) is a water-soluble analogue of camptothecin (cpt), an antitumor drug extracted from the chinese tree camptotheca acuminata. sn-38 is an active metabolite of cpt-11 that contributes significantly to its activity. the antitumor effects of cpt-11 and sn-38 are exerted through a novel mechanism of action; inhibition of dna topoisomerase i. cpt-11 and its metabolite have demonstrated potent inhibitory activity against a variety of cancer cell lines in vitro and against several mur ... | 1996 | 8633248 |
| stimulation of interleukin-1beta-converting enzyme activity during growth inhibition by cpt-11 in the human myeloid leukemia cell line k562. | camptothecin (cpt) was first extracted from camptotheca acuminata and has a strong antitumor effect. its water-soluble derivative, cpt-11, has higher therapeutic efficacy and less toxicity than cpt. recently, cpt-treated cells have been shown to undergo apoptosis. however, the mechanism of induction of apoptosis by cpt has not been characterized in detail in any type of cells. on the other hand, interleukin-1beta-converting enzyme (ice) is a mammalian homologue of ced3, a protein required for ap ... | 1996 | 8812723 |
| [camptothecin and derivatives: a new class of antitumor agents]. | camptothecin (cpt), an alkaloid isolated from the stem wood and bark of camptotheca acuminata native to china, was discovered in the early 60's after a systematic screening of natural products by the national cancer institute (nci). this new anticancer agent displays an unique mechanism of action as it inhibits intranuclear enzyme topoisomerase 1, involved in dna replication. cpt is poorly water soluble and causes severe and unpredictable toxicities such as haemorrhagic cystitis and diarrhea; fo ... | 1996 | 8965250 |
| reversed-phase high-performance liquid chromatography method for the simultaneous quantitation of the lactone and carboxylate forms of the novel natural product anticancer agent 10-hydroxycamptothecin in biological fluids and tissues. | camptothecins are indole alkaloids isolated from a chinese tree, camptotheca acuminata, and have a wide spectrum of anticancer activity in vitro and in vivo. a novel camptothecin congener 10-hydroxycamptothecin (hcpt) has been shown to be more active and less toxic than camptothecin, and the lactone hcpt is believed to be responsible for its anticancer activity. in the present study, a reversed-phase high-performance liquid chromatography, (hplc) with fluorescence detection was developed and val ... | 1996 | 8971608 |
| cloning and expression of a plant homologue of the small subunit of the golgi-associated clathrin assembly protein ap19 from camptotheca acuminata. | clathrin-coated vesicles (ccvs) are involved in selective protein transport in eukaryotes. ap-1 and ap-2 are protein complexes found in the ccvs of the golgi apparatus and the plasma membrane respectively. ap19 is the smallest polypeptide chain components of ap-1. we have identified a cdna clone (cap19) encoding a putative homologue for the assembly protein ap19 from the chinese medicinal tree, camptotheca acuminata. the deduced polypeptide contains 161 amino acids and has a predicted mr of 1882 ... | 1996 | 9002613 |
| camptothecin and taxol: from discovery to clinic. | camptothecin (cpt) and taxol are secondary metabolites found in the stembark of camptotheca acuminata, a native of china, and taxus brevifolia, found in the northwest pacific coastal region of the usa, respectively. the compounds were isolated through bioassay-guided fractionation of various extracts and through chromatographic fractions. their unique and hitherto unknown structures were elucidated by nuclear magnetic resonance, mass spectrometry and x-ray analysis. both compounds have unique me ... | 1996 | 9213622 |
| sustained harvest of camptothecin from the leaves of camptotheca acuminata. | over a 12-week period, new growth was collected at different intervals from camptotheca acuminata trees to determine whether a leaf harvest strategy would be an efficient means for the production of the alkaloid camptothecin. because camptothecin accumulates in young leaves and because the harvesting of young tissue stimulates axillary bud outgrowth, this strategy increased the harvestable amount of camptothecin from trees in a nondestructive manner. | 1997 | 9214735 |
| tryptophan decarboxylase is encoded by two autonomously regulated genes in camptotheca acuminata which are differentially expressed during development and stress. | camptothecin (cpt) is a valuable anti-cancer monoterpene alkaloid produced by the chinese tree camptotheca acuminata. tryptophan decarboxylase (tdc) supplies tryptamine for the indole moiety of cpt and its derivatives, and is considered a key step in monoterpene indole alkaloid biosynthesis as it links primary and secondary metabolism. this report describes the isolation and characterization of tdc1 and tdc2, two autonomously regulated tdc genes from camptotheca. when expressed in escherichia co ... | 1997 | 9225462 |
| molecular characterization of three differentially expressed members of the camptotheca acuminata 3-hydroxy-3-methylglutaryl coa reductase (hmgr) gene family. | camptotheca acuminata is a chinese tree that produces the anti-cancer monoterpenoid indole alkaloid camptothecin (cpt). 3-hydroxy-3-methylglutaryl coenzyme a reductase (hmgr) supplies mevalonate for the terpenoid moiety of cpt and its hydroxylated derivative 10-hydroxycamptothecin (10-oh-cpt). we previously described the isolation of a gene encoding hmgr from c. acuminata (hmg1) and analyzed its expression in transgenic tobacco [6]. here, we report on the isolation of genomic (hmg2) and cdna (hm ... | 1997 | 9278168 |
| topoisomerase i inhibitors: review and update. | this review presents a summary of preclinical and clinical data on the topoisomerase i (topo i) inhibitors that are under clinical development. to date, all of the topo i inhibitors that have been clinically evaluated are analogues of camptothecin, an extract of the chinese tree camptotheca acuminata. the therapeutic development of camptothecin was initially limited by its poor solubility and unpredictable toxicity. more recently, a number of water-soluble camptothecin analogues have undergone e ... | 1997 | 9358934 |
| preclinical pharmacology of the natural product anticancer agent 10-hydroxycamptothecin, an inhibitor of topoisomerase i. | 10-hydroxycamptothecin (hcpt) is an indole alkaloid isolated from a chinese tree, camptotheca acuminata, and has a wide spectrum of anticancer activity in vitro and in vivo mainly through inhibitory effects on topoisomerase i. hcpt has been shown to be more potent and less toxic than camptothecin and has recently undergone clinical trials. to determine how hcpt might be best used as an anticancer agent, preclinical studies of the pharmacokinetics, tissue distribution, metabolism and elimination ... | 1998 | 9488594 |
| camptothecin and taxol: discovery to clinic. | camptothecin (cpt) is a pentacyclic alkaloid isolated from wood and bark of camptotheca acuminata. initially it was found to be highly active in a number of mouse in vivo cancer assays. subsequently, cpt was found to uniquely inhibit an enzyme, topoisomerase i, which is involved in dna replication. a number of cpt analogs are in advanced clinical trial, and two, topotecan and cpt-11, have been approved for marketing by the fda. taxol, a taxane alkaloid, was isolated from taxus brevifolia. taxol ... | 1998 | 9735871 |
| the clinical pharmacology of topoisomerase i inhibitors. | the chinese tree camptotheca acuminata, or xi shu, brings us a unique class of chemotherapeutic agents known as the camptothecins. because the parent compound exhibited excessive toxicity and poor aqueous solubility, synthetic and semisynthetic analogs were developed. these compounds contain a lactone ring that is necessary for activity and is easily hydrolyzed into the less active hydroxy carboxylic acid. irinotecan, a semisynthetic analog is a prodrug that is cleaved by a carboxylesterase-conv ... | 1998 | 9779877 |
| tissue-specific expression of the beta-subunit of tryptophan synthase in camptotheca acuminata, an indole alkaloid-producing plant. | camptothecin is an anticancer drug produced by the monoterpene indole alkaloid pathway in camptotheca acuminata. as part of an investigation of the camptothecin biosynthetic pathway, we have cloned and characterized a gene from c. acuminata encoding the beta-subunit of tryptophan (trp) synthase (tsb). in c. acuminata tsb provides trp for both protein synthesis and indole alkaloid production and therefore represents a junction between primary and secondary metabolism. tsb mrna and protein were de ... | 1999 | 10318682 |
| cloning of the gene encoding 3-hydroxy-3-methylglutaryl coenzyme a reductase from terpenoid antibiotic-producing streptomyces strains. | we have isolated a mutant lacking 3-hydroxy-3-methylglutaryl coa (hmg-coa) reductase activity from a terpenoid antibiotic (terpentecin) producer, streptomyces griseolosporeus mf730-n6, which uses both the mevalonate and nonmevalonate pathways for the formation of isopentenyl diphosphate, by screening terpentecin non-producing mutants. terpentecin is known to be synthesized via the mevalonate pathway. the gene encoding hmg-coa reductase (hmgg) was cloned and identified by complementation of the m ... | 2000 | 10660057 |
| [irinotecan (topoisomerase-i inhibitor) for the treatment of recurrent primary intracranial malignant lymphoma]. | primary intracranial malignant lymphoma is a fetal disease with poor prognosis, and there is no effective treatment against recurrent primary intracranial malignant lymphomas. we report 3 cases of malignant lymphoma treated with irinotecan (topoisomerase-i inhibitor, camptothecin derivatives), an aromatic drug extracted from camptotheca acuminata. after the initial diagnosis, surgical resection followed by radiation therapy was performed for one cerebral, and two cerebellar malignant lymphomas. ... | 2000 | 10740645 |
| [determination of camptothecine in the fruit of camptotheca acuminata decne. by rp-hplc]. | a rp-hplc method wsa developed for the determination of camptothecine in the fruit of camptotheca acuminata, using ywg-c18 column and methanol-water(6:4) as the mobile phase with uv detection at 254 nm. the average recovery was 98.67% and rsd 1.71%. | 1997 | 10743218 |
| anti-cancer drug discovery and development in brazil: targeted plant collection as a rational strategy to acquire candidate anti-cancer compounds. | throughout medical history, plant products have been shown to be valuable sources of novel anti-cancer drugs. examples are the vinca: alkaloids, the taxanes, and the camptothecins, derived from the madagscan periwinkle plant catharantus roseus, the pacific yew taxus brevifolia, and the chinese tree camptotheca acuminata, respectively. for this reason, the south-american office for anti-cancer drug development has implemented a large-scale project of acquisition and testing of compounds isolated ... | 2000 | 10884497 |
| apoptosis induction and cell cycle perturbation in human hepatoma hep g2 cells by 10-hydroxycamptothecin. | 10-hydroxycamptothecin (hcpt), a dna topoisomerase i inhibitor, is an antitumor alkaloid isolated from a chinese tree, camptotheca acuminata, and exhibits a remarkable antihepatoma effect. we studied hcpt to determine whether or not its anti-hepatoma activity occurs through apoptosis induction and cell cycle disturbance using the mtt method, dapi staining, agarose gel electrophoresis and flow cytometric analysis. the results showed that hcpt inhibited proliferation of human hepatoma hep g2, bel- ... | 1999 | 10885905 |
| therapeutic applications of medicinal plants in the treatment of breast cancer: a review of their pharmacology, efficacy and tolerability. | various active compounds (or their semi-synthetic derivatives) derived from medicinal plants have been assessed for their efficacy and tolerability in the treatment of breast cancer. some of these plant species, including taxus baccata (paclitaxel, docetaxel), podophyllum peltatum (etoposide), camptotheca acuminata (camptothecin) and vinca rosea (vinblastine, vinorelbine) have well recognized antitumour activity in breast cancer, and have been evaluated in clinical trials. for example, results f ... | 2000 | 11059361 |
| cisplatin and irinotecan in upper gastrointestinal malignancies. | irinotecan (cpt-11, camptosar) a topoisomerase i inhibitor derived from the chinese shrub camptotheca acuminata, has broad activity in varied gastrointestinal malignancies, including pancreatic, biliary, esophageal, and stomach cancers. using cisplatin (platinol) plus irinotecan as a backbone for chemotherapy, a combination for which in vitro synergy and possible sequence dependency have been identified, several clinical trials are being conducted combining these two drugs with other chemotherap ... | 2001 | 11301840 |
| rapid micro-assay of camptothecin in camptotheca acuminata. | a micro-assay has been developed to extract and rapidly quantify the anticancer alkaloid, camptothecin (cpt), from two leaf disks of camptotheca acuminata decaisne (nyssaceae). this assay utilizes thin-layer chromatography in conjunction with fluorescence imaging to obtain reproducible measurements in the nanogram range. a large number of trees can be screened using this procedure to identify high producers of cpt in a relatively short period of time. | 2001 | 11458464 |
| advances in cancer therapy with plant based natural products. | natural products have long been a fertile source of cure for cancer, which is projected to become the major causes of death in this century. however, there is a continuing need for development of new anticancer drugs, drug combinations and chemotherapy strategies, by methodical and scientific exploration of enormous pool of synthetic, biological and natural products. there are at least 250,000 species of plants out of which more than one thousand plants have been found to possess significant ant ... | 2001 | 11562277 |
| bcmfs1, a novel major facilitator superfamily transporter from botrytis cinerea, provides tolerance towards the natural toxic compounds camptothecin and cercosporin and towards fungicides. | bcmfs1, a novel major facilitator superfamily gene from botrytis cinerea, was cloned, and replacement and overexpression mutants were constructed to study its function. replacement mutants showed increased sensitivity to the natural toxic compounds camptothecin and cercosporin, produced by the plant camptotheca acuminata and the plant pathogenic fungus cercospora kikuchii, respectively. overexpression mutants displayed decreased sensitivity to these compounds and to structurally unrelated fungic ... | 2002 | 12324349 |
| metabolite profiling of alkaloids and strictosidine synthase activity in camptothecin producing plants. | camptothecin derivatives are clinically used anti-neoplastic alkaloids that biogenetically belong to monoterpenoid indole alkaloids. camptothecin-related alkaloids from the methanol extracts of ophiorrhiza pumila, camptotheca acuminata and nothapodytes foetida plants were profiled and identified using a reverse-phase high performance liquid chromatography coupled with on-line photodiode array detection and electrospray-ionization ion-trap mass spectrometry. a natural 10-glycosyloxy camptothecin, ... | 2003 | 12620359 |
| variations in the secondary metabolite camptothecin in relation to tissue age and season in camptotheca acuminata. | we investigated variation in concentration of the secondary metabolite, camptothecin (cpt), in relation to leaf, branch and tree age, season, and leaf drying method in camptotheca acuminata decaisne saplings. younger leaves contained higher cpt concentrations than older leaves. within a branch, there was a linear decline in cpt concentration from leaves at the apex of the branch down to leaf 7. comparing leaves of similar age, those from younger trees had higher cpt concentrations than those fro ... | 1998 | 12651381 |
| the emerging role of irinotecan (cpt-11) in the treatment of malignant glioma in brain tumors. | irinotecan is a water-soluble derivative of camptothecin, an alkylator originally extracted from the chinese tree camptotheca acuminata. laboratory studies have demonstrated the activity of irinotecan in a broad panel of pediatric and adult central nervous system tumor xenografts in athymic nude mice. these studies led to a phase ii trial that confirmed the activity of this agent in the treatment of recurrent malignant glioma. subsequent laboratory studies have demonstrated that a combination of ... | 2003 | 12712457 |
| [topotecan for pediatric patients with resistant and recurrent solid tumors]. | topotecan is a cytotoxic drug isolated from the camptotheca acuminata tree (from china). it is able to block the enzyme dna topoisomerase i and has recently been used in the treatment of pediatric cancer. | 2003 | 12882743 |
| camptothecin and 10-hydroxycamptothecin from camptotheca acuminata hairy roots. | camptothecin (cpt) is an anticancer and antiviral alkaloid produced by the chinese tree camptotheca acuminata (nyssaceae) and some other species belonging to the families apocynaceae, olacaceae, and rubiaceae. bark and seeds are currently used as sources for the drug. several attempts have been made to produce cpt from cell suspensions; however, the low yields obtained limit this approach. cultures of differentiated cell types may be an alternative source of alkaloid production. hairy root cultu ... | 2004 | 13680137 |
| [improved camptothecin production by cell lines of camptotheca acuminata]. | the concentration of camptothecin was determined in different tissues of camptotheca acuminata seedling. the concentrations of camptothecin in new leaves and roots were significantly higher than in other tissues. however, the concentration of camptothecin declined with leaves becoming old. the induction of callus and cell suspension cultures from younger leaves of camptotheca acuminata was observed. cell lines were selected with improved camptothecin production as 0.02%. | 2003 | 14574990 |
| current treatment and future directions in neuroblastoma. | the international neuroblastoma staging system (inss) and pathology classification (inpc) were applied to analyze the results of treatment of 644 patients with neuroblastoma treated in japan during the years from 1995 to 1999, and it was found that the pathology classification (inpc) showed the strongest relevance to prognosis compared to other factors such as stage, mync amplification, dna ploidy and 1p-deletion. current results of treatment for advanced neuroblastoma are still not satisfactory ... | 2003 | 14649477 |
| camptothecin and taxol: historic achievements in natural products research. | the research team of dr. monroe e. wall and dr. mansukh c. wani of research triangle institute discovered two first-in-class life-saving chemotherapeutic agents. camptothecin, first isolated and identified from camptotheca acuminata, was found to kill cancer cells uniquely via topoisomerase i poisoning. presently, two first-generation analogues of camptothecin are used to treat ovarian, colorectal, and small-cell lung cancers, and several second-generation analogues are in clinical trials. taxol ... | 2004 | 14987046 |
| pharmacology of irinotecan. | irinotecan (cpt-11) is a semisynthetic derivative of camptothecin, an alkaloid extracted from the chinese plant camptotheca acuminata. it bears a bis-piperidine moiety and was selected for its water solubility and promising preclinical antitumor activity in in vitro and in vivo models. the target of drugs of the camptothecin family is dna topoisomerase i, a nuclear enzyme involved in the relaxation of the dna double helix required for replication and transcription activities. they stabilize the ... | 1998 | 14988754 |
| rubitecan: 9-nc, 9-nitro-20(s)-camptothecin, 9-nitro-camptothecin, 9-nitrocamptothecin, rfs 2000, rfs2000. | rubitecan [orathecin, 9-nitrocamptothecin, 9nc, rfs 2000] is a topoisomerase i inhibitor extracted from the bark and leaves of the camptotheca acuminata tree, which is native to china. rubitecan is an oral compound being developed for the treatment of pancreatic cancer and other solid tumours by supergen. one of the major benefits of rubitecan is that it can be administered in an outpatient setting, so patients can be treated in their homes. rubitecan was isolated by the stehlin foundation in th ... | 2004 | 15357630 |
| camptothecin, over four decades of surprising findings. | camptothecin (cpt) is a modified monoterpene indole alkaloid produced by camptotheca acuminata (nyssaceae), nothapodytes foetida, pyrenacantha klaineana, merrilliodendron megacarpum (icacinaceae), ophiorrhiza pumila (rubiaceae), ervatamia heyneana (apocynaceae) and mostuea brunonis (gelsemiaceae), species belonging to unrelated orders of angiosperms. from the distribution of cpt and other secondary metabolites, it has been postulated that the genes encoding enzymes involved in their biosynthesis ... | 2004 | 15474560 |
| cellular localisation of the anti-cancer drug camptothecin in camptotheca acuminata decne (nyssaceae). | in camptotheca acuminata, we studied the cellular sites of accumulation of the alkaloid camptothecin (cpt), in both plants grown in the field and those grown in a greenhouse, subjecting the latter to stress (i.e., draught, nutritional deficit, and pruning). fresh sections of the leaf, stem, and root were analysed for the presence of cpt by examining the autofluorescence that the cpt molecule emits when exposed to uv radiation. in the plants grown in the field, cpt was observed only rarely. in th ... | 2004 | 15596415 |
| improvement of growth and camptothecin yield by altering nitrogen source supply in cell suspension cultures of camptotheca acuminata. | nitrate at 70 mm gave the highest biomass of camptotheca acuminata in suspension culture in ms medium, but a nh4+/no3- molar ratio of 5:1 (giving a total of 40 mm n) gave the maximum camptothecin yield. a two-stage flask culture system was established to improve culture efficiency; cell dry weight, camptothecin content and yield was increased by 30%, 280% and 340%, respectively when compared with those of control, reaching up to 36 g l(-1), 0.36 mg g(-1), and 12.8 mg l(-1), respectively. | 2004 | 15604829 |
| [accumulation and localization of camptothecin in young shoot of camptotheca acuminata]. | the developmental of young stems and leaves were investigated using optical, fluorescence and scanning electron microscopy and the camptothecin content in camptotheca acuminata was analyzed by hplc. secretory structure, especially secretory canals were found. a linear relationship (r(2)=0.9257) was found between cpt content and secretory canal density of stem. the secretion in canals and glandular trichomes showed intense blue autofluorescence under 360 nm uv light. the results showed that campt ... | 2004 | 15627689 |
| antifungal activity of camptothecin, trifolin, and hyperoside isolated from camptotheca acuminata. | leaf spots and root rots are major fungal diseases in camptotheca acuminata that limit cultivation of the plant for camptothecin (cpt), a promising anticancer and antiviral alkaloid. bioassays showed that pure cpt and flavonoids (trifolin and hyperoside) isolated from camptotheca effectively control fungal pathogens in vitro, including alternaria alternata, epicoccum nigrum, pestalotia guepinii, drechslera sp., and fusarium avenaceum, although antifungal activity of these compounds in the plant ... | 2005 | 15631505 |
| new camptothecin and ellagic acid analogues from the root bark of camptotheca acuminata. | as part of a study on chemical constituents of camptotheca species, one new natural camptothecin analogue (2), two new alkaloids (3, 4), one new ellagic acid analogue (5), and 19 known compounds (1, 6-23) have been isolated from the root bark, stem bark, fruits, and leaves of camptotheca acuminata decaisne. the structures of 2-5 were determined from spectral data to be 10-methoxy-20-o-acetylcamptothecin (2), 20-o-beta-glucopyranosyl 18-hydroxycamptothecin (3), 20-formylbenz indolizino [1,2-b]qui ... | 2004 | 15643560 |
| molecular characterization of two anthranilate synthase alpha subunit genes in camptotheca acuminata. | the potent anticancer and antiviral compound camptothecin (cpt) is a monoterpene indole alkaloid produced by camptotheca acuminata. in order to investigate the biosynthetic pathway of cpt, we studied the early indole pathway, a junction between primary and secondary metabolism, which generates tryptophan for both protein synthesis and indole alkaloid production. we cloned and characterized the alpha subunit of anthranilate synthase (asa) from camptotheca (designated caasa), catalyzing the first ... | 2005 | 15645305 |
| the effect of growth regulators and sucrose on anthocyanin production in camptotheca acuminata cell cultures. | the effect of different concentrations of growth regulators and sucrose on anthocyanin production in cell suspension cultures of camptotheca acuminata decaisne (nyssaceae) was described for the first time and qualitatively and quantitatively evaluated. anthocyanin production was significantly greater in the presence of kinetin, compared to benzyladenine, with the greatest concentration observed in the presence of 2 microm kinetin. no significant differences in anthocyanin production were observe ... | 2005 | 15854838 |
| camptothecin and its analogues: a review on their chemotherapeutic potential. | topoisomerase i (topo-i) is a major target for anticancer drug discovery and design. as a result, topo-i inhibitors constitute an important class of the current anticancer drugs. to date, all of the topo-i inhibitors that have been clinically evaluated are analogues of camptothecin (cpt), an extract of the chinese tree camptotheca acuminata. cpt has shown significant antitumor activity to lung, ovarian, breast, pancreas and stomach cancers. in this article the, phytochemical aspect, and various ... | 2005 | 15938148 |
| an ab initio quantum mechanics calculation that correlates with ligand orientation and dna cleavage site selectivity in camptothecin-dna-topoisomerase i ternary cleavage complexes. | camptothecin (cpt), a cytotoxic natural alkaloid isolated from camptotheca acuminata, and its derivatives represent an important class of cancer chemotherapeutic drugs that act by inhibiting topoisomerase i (top1). the mechanism of top1 inhibition by cpt has been determined by x-ray crystallography. biochemical studies carried out both in vitro and in vivo indicated that cpt has strict dna sequence preference for -1 t and strong preference for +1 g at the cleavage site. to understand the molecul ... | 2005 | 16011334 |
| wound-induced expression of the ferulate 5-hydroxylase gene in camptotheca acuminata. | the phenylpropanoid pathway plays important roles in plants following exposure to environmental stresses, such as wounding and pathogen attack, which lead to the production of a variety of compounds, including lignin, flavonoids and phytoalexins. ferulate 5-hydroxylase (f5h) is a cytochrome p450-dependent monooxygenase that catalyses the hydroxylation of ferulic acid, coniferaldehyde and coniferyl alcohol, leading to sinapic acid and syringyl lignin biosynthesis. we isolated f5h cdna and genomic ... | 2006 | 16332414 |
| laticifers in camptotheca acuminata decne: distribution and structure. | in this paper, a system of laticifers in camptotheca acuminata decne (nyssaceae) is described. laticifers were already present in the leaf primordia of the shoot apex. in the mature leaves, laticifers were found in the midrib and in the larger veins, both in the parenchymatic region delimited by vascular bundles and in the cortex just external to the phloem. in the stem, laticifers were present in both the primary and secondary body, running parallel to the longitudinal axis. they were located i ... | 2005 | 16333574 |
| concise synthesis of 22-hydroxyacuminatine, cytotoxic camptothecinoid from camptotheca acuminata, by pyridone benzannulation. | a short, efficient synthesis of 22-hydroxyacuminatine, starting from a readily accessible hydroxy pyridone, is presented; key steps include a heck coupling with methyl pentadienoate, a flash vacuum pyrolytic cyclization, and a friedländer condensation. | 2006 | 16446797 |
| molecular cloning and characterization of a novel stem-specific gene from camptotheca acuminata. | in higher plants, p450s participate in the biosynthesis of many important secondary metabolites. here we reported for the first time the isolation of a new cytochrome p450 cdna that expressed in a stem-specific manner from camptotheca acuminata (designated as cass), a native medicinal plant species in china, using race-pcr. the full-length cdna of cass was 1735 bp long containing a 1530 bp open reading frame (orf) encoding a polypeptide of 509 amino acids. bioinformatic analysis revealed that ca ... | 2006 | 16466640 |
| total synthesis and biological evaluation of 22-hydroxyacuminatine. | a total synthesis of 22-hydroxyacuminatine, a cytotoxic alkaloid isolated from camptotheca acuminata, is reported. the key step in the synthesis involves the reaction of 2,3-dihydro-1h-pyrrolo[3,4-b]quinoline with a brominated phthalide to generate a substituted pentacyclic 12h-5,11a-diazadibenzo[b,h]fluoren-11-one intermediate. despite its structural resemblance to camptothecin and luotonin a, a biological evaluation of 22-hydroxyacuminatine in a topoisomerase i-deficient cell line p388/cpt45 h ... | 2006 | 16480276 |
| triterpenoids and ellagic acid derivatives from in vitro cultures of camptotheca acuminata decaisne. | the metabolic profile of secondary products in calli and cell suspension cultures of camptotheca acuminata decaisne was investigated and compared to that of the leaves and roots taken from the plant. neither in vitro system produced the anticancer quinoline alkaloid camptothecin (cpt); they accumulated discrete quantities of polyhydroxylated triterpenoids, different from those found in the plant organs, and ellagic acid derivatives. nine ellagic acid derivatives (1a-1d and 2a-2e) and eight trite ... | 2006 | 16762560 |
| [effects of cu2+ on biosynthesis of camptothecin in cell cultures of camptotheca acuminata]. | camptothecin is a strong anti-tumor compound isolated from camptotheca acuminata. one of the most important way for the production of camptothecin is by cell cultures of camptotheca acuminata. the effect of cu2+ on camptothecin accumulation in camptotheca acuminata cell line was described in this paper. the results showed that the optimum cucl2 concentration in b5 medium was 0.008 mg/ml, which increased camptothecin production for 30 times compare to the control while has no inhibitive effects o ... | 2006 | 16894899 |
| extraction and composition of three naturally occurring anti-cancer alkaloids in camptotheca acuminata seed and leaf extracts. | naturally occurring camptothecins (cpt) are important sources of chemotherapeutic agents for clinical treatment of cancer. extraction of cpt from camptotheca acuminata trees remains to be a cost-effective way in the supply equation compared with a total synthesis. this study conducted a series of experiments to determine efficient solvent for the maximal extraction of cpt and its two derivatives, hydroxycamptothecin (hcpt) and methoxycamptothecin, from seeds and leaves of c. acuminata. methanol ... | 2007 | 17137773 |
| molecular cloning, expression profiling and functional analysis of a dxr gene encoding 1-deoxy-d-xylulose 5-phosphate reductoisomerase from camptotheca acuminata. | as the second enzyme of the non-mevalonate terpenoid pathway for isopentenyl diphosphate biosynthesis, dxp reductoisomerase (dxr, ec: 1.1.1.267) catalyzes a committed step of the mep pathway for camptothecin (cpt) biosynthesis. in order to understand more about the role of dxr involved in the cpt biosynthesis at the molecular level, the full-length dxr cdna sequence (designated as cadxr) was isolated and characterized for the first time from a medicinal nyssaceae plant species, camptotheca acumi ... | 2008 | 17257708 |
| characteristics of the microbial community in rhizosphere of camptotheca acuminata cultured with exotic invasive plant eupatorium adenophorum. | the traditional culture-dependent plate counting and culture-independent small-subunit-ribosomal rna gene-targeted molecular techniques, single-strand conformation polymorphism (sscp) and terminal restriction fragment length polymorphism (trflp) combined with 16s rdna clone library were adopted to investigate the impacts of secretion from camptotheca acuminata (abbreviated to ca) roots on the quantities and structure of eukaryotic microbes and bacteria in the rhizosphere, and the possibility tha ... | 2007 | 17393079 |
| molecular target-guided tumor therapy with natural products derived from traditional chinese medicine. | a tremendous interest exists in the western world in traditional chinese medicine (tcm) with rapidly increasing export rates of tcm products from china to europe and usa. this led to a national decision of the chinese government to implement a "plan for the modernization of chinese medicine". concerning the use of chinese medicinal herbs, two major directions can be distinguished. one field is phytochemistry and pharmacognosy. secondary metabolites isolated from chinese plants can be easily subj ... | 2007 | 17691944 |
| camptothecin: therapeutic potential and biotechnology. | camptothecin (cpt) and its derivatives have been received considerable attention recently. two semi-synthetic derivatives, topotecan and irinotecan, are currently prescribed as anticancer drugs. several more are now in clinical trial. cpt is produced in many plants belonging to unrelated orders of angiosperms. at present, cpt supplied for pharmaceutical use is extracted from the plants, camptotheca acuminata and nothapodytes foetida. several efforts have been made to sustain a stable production ... | 2007 | 17691988 |
| [callus induction and cultivation of camptotheca acuminata]. | to study the callus induction from leaf, stem segments and stem segments with axillary's bud and the subculture conditions of callus in camptotheca acuminata. | 2007 | 17879723 |
| cpt accumulation in the fruit and during early phases of plant development in camptotheca acuminata decaisne (nyssaceae). | we describe the dynamics of camptothecin (cpt) accumulation during the early phases of plant development in camptotheca acuminata. tlc and hplc analyses were performed on the entire mature fruit and all of its parts and on the organs of seedlings in different developmental stages. in the mature fruit, the cpt content was relatively high (2.83 mg g(-1) dw); it was accumulated especially in the endosperm (1.82 mg g(-1) dw) and embryo (1.10 mg g(-1) dw). regarding seedlings, cpt was present in all ... | 2007 | 18075887 |
| potential of poly(amidoamine) dendrimers as drug carriers of camptothecin based on encapsulation studies. | camptothecin (cpt), a plant alkaloid isolated from camptotheca acuminata, has an extremely low solubility in aqueous medium, which presents a major challenge during drug formulation in clinical trails. in the present study we investigated the potential of poly(amidoamine) (pamam) dendrimers as drug carriers of cpt through aqueous solubility studies. results showed that the aqueous solubility of cpt was significantly increased by pamam dendrimers. the effect of pamam generation on cpt solubility ... | 2008 | 18215444 |
| a new isopentenyl diphosphate isomerase gene from camptotheca acuminata: cloning, characterization and functional expression in escherichia coli. | isopentenyl diphosphate isomerase (ec 5.3.3.2, ipi) catalyzes the revisable conversion of 5-carbon isopentenyl diphosphate (ipp) and its allylic isomer dimethylallyl diphosphate (dmapp), which are the essential precursors for isoprenoids, including anti-tumor camptothecin. here we report cloning, characterization and functional expression of a new cdna encoding ipi from camptotheca acuminata. the full-length cdna was 1143 bp long designated as caipi (genbank accession number: dq839416), containi ... | 2008 | 18297601 |
| molecular cloning and characterization of 1-hydroxy-2-methyl-2-(e)-butenyl 4-diphosphate reductase (cahdr) from camptotheca acuminata and its functional identification in escherichia coli. | camptothecin is an anti-cancer monoterpene indole alkaloid. the gene encoding 1-hydroxy-2-methyl-2-(e)-butenyl 4-diphosphate reductase (designated as cahdr), the last catalytic enzyme of the mep pathway for terpenoid biosynthesis, was isolated from camptothecin-producing camptotheca acuminata. the full-length cdna of cahdr was 1686 bp encoding 459 amino acids. comparison of the cdna and genomic dna of cahdr revealed that there was no intron in genomic cahdr. southern blot analysis indicated that ... | 2008 | 18315946 |
| mutations in topoisomerase i as a self-resistance mechanism coevolved with the production of the anticancer alkaloid camptothecin in plants. | plants produce a variety of toxic compounds, which are often used as anticancer drugs. the self-resistance mechanism to these toxic metabolites in the producing plants, however, remains unclear. the plant-derived anticancer alkaloid camptothecin (cpt) induces cell death by targeting dna topoisomerase i (top1), the enzyme that catalyzes changes in dna topology. we found that cpt-producing plants, including camptotheca acuminata, ophiorrhiza pumila, and ophiorrhiza liukiuensis, have top1s with poi ... | 2008 | 18443285 |
| [effect of nitrogen on camptothecin content in camptotheca acuminata seedlings]. | to investigate the effects of nitrogen concentration on the camptothecin (cpt) content in camptotheca acuminata seedlings: | 2008 | 18533483 |
| micropropagation and production of camptothecin from in vitro plants of ophiorrhiza rugosa var. decumbens. | camptothecin and its derivatives are used as anticancer alkaloids. at present, they are obtained by the extraction from the chinese tree camptotheca acuminata and the indigenous tree nothapodytes foetida. identification of alternate species of plants like ophiorrhiza species and development of tissue culture methods may be a suitable alternative for large-scale micropropagation as well as for the production of camptothecin. plantlets were successfully regenerated from shoot cultures of ophiorrhi ... | 2008 | 18780241 |
| [the study of dynamic acccumulation of camptothecin in camptotheca acuminata fruit by tlcs]. | to establish tlc scanning method for the determination of camptothecin in camptotheca acuminata fruit, and analysis the dynamic accumulation of camptothecin in camptotheca acuminata fruit to find out the best collection period. | 2008 | 18826145 |
| [effects of nitrogen forms on camptothecin content and its metabolism-related enzymes activities in camptotheca acuminata seedlings]. | to investigate the effects of nitrogen forms on the camptothecin (cpt) content, tryptophan synthase (tsb) and tryptophan decarboxylase (tdc) activities in camptotheca acuminata seedlings. | 2008 | 18837304 |
| molecular cloning, characterization and expression of a jasmonate biosynthetic pathway gene encoding allene oxide cyclase from camptotheca acuminata. | aoc (allene oxide cyclase; ec 5.3.99.6), an essential enzyme in jasmonic acid and its methyl ester biosynthesis, was cloned from camptotheca acuminata (named as caaoc), a native medicinal plant species in china. caaoc had significant similarity at the amino-acid level with aocs from other plant species. comparison between the sequences of the full-length cdna and genomic dna of caaoc revealed that the genomic dna of caaoc contained an 89-bp intron and a 240-bp intron. southern-blot analysis indi ... | 2008 | 18847436 |
| allene oxide cyclase from camptotheca acuminata improves tolerance against low temperature and salt stress in tobacco and bacteria. | allene oxide cyclase (aoc, e 5.3.99.6) is an essential enzyme in jasmonate (ja) biosynthetic pathway. an aoc gene (defined as caaoc, database accession no. ay863428) had been isolated from camptotheca acuminata in previous work. real-time quantitative pcr analysis indicated that mrna expression of caaoc was induced by salt stress (120 mm nacl) and low temperature (4 degrees c). in order to further investigate the role of aoc gene in the processes, caaoc was introduced into tobacco via agrobacter ... | 2009 | 18850307 |
| an endophytic fungus from camptotheca acuminata that produces camptothecin and analogues. | the pentacyclic quinoline alkaloid camptothecin (1) is a potent antineoplastic agent. two of its analogues, 9-methoxycamptothecin (2) and 10-hydroxycamptothecin (3), exhibit similar potency but do not have the potential therapeutic drawbacks produced by unmodified 1. we have established methodology for the isolation and unequivocal identification and characterization of a novel endophytic fungus isolated from the inner bark of the medicinal plant camptotheca acuminata, which produced 1-3 in rich ... | 2009 | 19119919 |
| [isolation and purification of 10-hydroxycamptothecin and vincoside-lactam from camptotheca acuminata seed by polyamide]. | to investigate the technological parameters of the isolation and purification of 10-hydroxycamptothecin and vincoside-lactam from camptotheca acuminata seed by polyamide. the static arid dynamic adsorption characteristics of 10-hydroxycamptothecin and vincoside-lactam on polyamide were studied, and the contents were determined by hplc. the optimum parameters for adsorption were as follows: the contents of 10-hydroxycamptothecin and vincoside-lactam in the extracts were 0.189 g x l(-1) and 0.334 ... | 2008 | 19149254 |
| novel camptothecin derivatives as topoisomerase i inhibitors. | camptothecin (cpt), a pentacyclic alkaloid isolated by wall et al. in 1958 from the chinese tree camptotheca acuminata, was reported to possess an interesting antitumor activity. late in 1985, it was reported by liu et al. that the cytotoxic activity of cpt was attributed to a novel mechanism of action involving the nuclear enzyme classified as type i dna topoisomerase. since the explanation of the unique mechanism of action, many derivatives have been synthesized and some of them are in various ... | 2009 | 19441934 |
| metabolite fingerprinting of camptotheca acuminata and the hplc-esi-ms/ms analysis of camptothecin and related alkaloids. | the major phytochemical constituents, namely, alkaloids, flavonoids and ellagic acid derivatives, of leaves of camptotheca acuminata were identified using high performance liquid chromatography (hplc) coupled with electrospray mass spectrometry (esi-ms) in extracts of plants cultivated in italy and collected at different growth stages. alkaloids related to camptothecin were identified and quantified by hplc coupled with esi-tandem mass spectrometry (ms/ms) employing, respectively, an ion trap an ... | 2010 | 19520541 |
| camptothecin production by in vitro cultures and plant regeneration in ophiorrhiza species. | camptothecin derivatives are clinically used for the treatment of various human cancers. these derivatives are semi-synthesized from camptothecin which is isolated from the extracts of camptotheca acuminata and nothapodytes foetida. for the feasible production of camptothecin, the protocols for the tissue cultures of ophiorrhiza species, o. pumila, o. liukiuensis and o. kuroiwai, have been established. the established aseptic plants and hairy roots produced camptothecin, and o. pumila hairy root ... | 2009 | 19521857 |
| 10-hydroxycamptothecin produced by a new endophytic xylaria sp., m20, from camptotheca acuminata. | a new 10-hydroxycamptothecin (hcpt)-producing fungus was isolated from camptotheca acuminata. the strain was classified as a xylaria sp. based on the internal transcribed spacer and 18s rdna gene analysis. all elicitors tested, except methyl jasmonate, increased hcpt production in submerged culture. the maximum yield was 5.4 mg hcpt/l(-1), when salicylic acid was added at 0.1 mm to the culture medium. | 2010 | 20112128 |
| cell-specific expression of tryptophan decarboxylase and 10-hydroxygeraniol oxidoreductase, key genes involved in camptothecin biosynthesis in camptotheca acuminata decne (nyssaceae). | camptotheca acuminata is a major natural source of the terpenoid indole alkaloid camptothecin (cpt). at present, little is known about the cellular distribution of the biosynthesis of cpt, which would be useful knowledge for developing new strategies and technologies for improving alkaloid production. | 2010 | 20403175 |
| rhizobium kunmingense sp. nov., isolated from rhizosphere soil of camptotheca acuminata decne. | strain lxd30(t) was isolated from rhizosphere soil of a plant of the species camptotheca acuminata decne which is native to warm, humid stream banks in southern china. analysis of the 16s rrna gene sequence revealed that the gram-negative, rod-shaped bacterium fell within the realm of the genus rhizobium and was most closely related to rhizobium huautlense so2(t) (96.4% sequence similarity) and rhizobium cellulosilyticum lmg 23642(t) (96.4%). the isolate grew optimally at ph7.0 and 25-28 degrees ... | 2010 | 20513962 |
| evaluation of antimicrobial activity of endophytic fungi from camptotheca acuminata (nyssaceae). | agricultural research of plant-derived endophytic fungi has grown in recent decades. we isolated 26 endophytic fungi from the leaves, stems and fruits of "the tree of life", camptotheca acuminata, and tested them for antimicrobial activities based on growth inhibition measurements in a modified agar diffusion method. fermentation broths from most of the isolates exhibited antifungal activity and 50% exhibited antibacterial activity; some of them also exhibited strong broad-spectrum antimicrobial ... | 2010 | 21038296 |
| correlation of camptothecin-producing ability and phylogenetic relationship in the genus ophiorrhiza. | camptothecin (cpt) is an essential precursor of semisynthetic chemotherapeutic agents for cancers throughout the world. in spite of the rapid growth of market demand, cpt raw material is still harvested by extraction from camptotheca acuminata and nothapodytes foetida because its total synthesis is not cost-effective. in this study, we examined eight species of the genus ophiorrhiza (rubiaceae) from thailand as novel alternative sources of cpt. cpt and/or 9-methoxy camptothecin (9-mcpt) were det ... | 2010 | 21104605 |
| correlations between camptothecin and related metabolites in camptotheca acuminata reveal similar biosynthetic principles and in planta synergistic effects. | camptothecin (cpt), 9-methoxycamptothecin (9-meo-cpt), and 10-hydroxycamptothecin (10-oh-cpt) are potent antineoplastic metabolites. we analyzed these metabolites in camptotheca acuminata sampled from germany and china, using lc-ms/ms and lc-esi-hrms/ms, coupled with chemometrics. multivariate analysis revealed that fresh stems of c. acuminata from china had the highest comprehensive metabolite load. significant positive correlations of cpt with 9-meo-cpt and 10-oh-cpt were observed by kruskal's ... | 2011 | 21238548 |
| nitrate reductase-mediated nitric oxide generation is essential for fungal elicitor-induced camptothecin accumulation of camptotheca acuminata suspension cell cultures. | secondary metabolite accumulation and nitric oxide (no) generation are two common responses of plant cells to fungal elicitors, and no has been reported to play important roles in elicitor-induced secondary metabolite production. however, the source of elicitor-triggered no generation in plant cells remains largely unknown. to investigate the origin of elicitor-triggered no, we examined nitrate reductase (nr) activities and the expression levels of nia1 and nia2 genes of camptotheca acuminata ce ... | 2011 | 21336687 |
| effect of artificial reconstitution of the interaction between the plant camptotheca acuminata and the fungal endophyte fusarium solani on camptothecin biosynthesis. | fungal endophytes inhabit healthy tissues of all terrestrial plant taxa studied and occasionally produce host-specific compounds. we recently isolated an endophytic fungus, fusarium solani, from camptotheca acuminata, capable of biosynthesizing camptothecin (cpt, 1), but this capability substantially decreased on repeated subculturing. the endophyte with an impaired 1 biosynthetic capability was artificially inoculated into the living host plants and then recovered after colonization. although t ... | 2011 | 21348469 |
| examination of camptothecin and 10-hydroxycamptothecin in camptotheca acuminata plant and cell culture, and the affected yields under several cell culture treatments. | camptothecin and its derivatives are monoterpenoid indole alkaloids exhibiting significant anti-tumor actions. with the aim of improving the production of these pharmaceuticals, the contents of camptothecin and 10-hydroxycamptothecin in different tissues including roots, stems, leaves, young flower buds, opening flowers, fading flowers and seeds from camptotheca acuminata, were investigated. the young flower buds had the highest alkaloid concentrations (camptothecin, 2.46 mg/g of dry weight; 10- ... | 2010 | 21443144 |
| regression of human colon cancer xenografts in scid mice following oral administration of water-insoluble camptothecins. | gastrointestinal cancers pose major public health problems worldwide, in part because little progress has been made in the treatment of colorectal cancers. the present study explored the potential use of natural product topoisomerase i inhibitors, 10-hydroxycamptothecin (hcpt) and camptothecin (cpt), in the treatment of human colon cancers. hcpt and cpt are indole alkaloids originally isolated from th. chinese tree, camptotheca acuminata. they have been shown to have a wide spectrum of anticance ... | 1997 | 21533469 |
| antitumor activity and pharmacokinetics following oral administration of natural product dna topoisomerase i inhibitors 10-hydroxycamptothecin and camptothecin in scid mice bearing human breast cancer xenografts. | the dna topoisomerase i inhibitors, 10-hydroxycamptothecin (hcpt) and camptothecin (cpt), are indole alkaloids isolated from the chinese tree, camptotheca acuminata. they have been shown to have a wide spectrum of anticancer activity both in vitro and in vivo. however, their use has been limited due to their water-insolubility. the purpose of the present study was 2-fold, to determine the in vitro and in vivo activity of hcpt and cpt against human breast cancer and to determine the pharmacokinet ... | 1997 | 21533497 |
| plantactinospora endophytica sp. nov., a novel actinomycete isolated from camptotheca acuminata decne., reclassification of actinaurispora siamensis as plantactinospora siamensis comb. nov. and emended description of the genus plantactinospora. | a novel endophytic actinomycete, designated yim 68255t, was isolated from healthy leaves of camptotheca acuminata decne. collected in yunnan province, south-west china and characterized by using a polyphasic approach. the strain formed well-developed substrate mycelia, but no aerial mycelium. it grew at 10-45 °c, ph 5-10 (optimum ph 7) and 0-3% (w/v) nacl. the dna g+c content was 73.0 mol%. phylogenetic analyses showed that strain yim 68255t belongs to the genus plantactinospora. however, it exh ... | 2011 | 22140153 |
| Pyrosequencing of the Camptotheca acuminata transcriptome reveals putative genes involved in camptothecin biosynthesis and transport. | ABSTRACT: | 2011 | 22035094 |
| development of transcriptomic resources for interrogating the biosynthesis of monoterpene indole alkaloids in medicinal plant species. | the natural diversity of plant metabolism has long been a source for human medicines. one group of plant-derived compounds, the monoterpene indole alkaloids (mias), includes well-documented therapeutic agents used in the treatment of cancer (vinblastine, vincristine, camptothecin), hypertension (reserpine, ajmalicine), malaria (quinine), and as analgesics (7-hydroxymitragynine). our understanding of the biochemical pathways that synthesize these commercially relevant compounds is incomplete due ... | 2012 | 23300689 |