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    Camptothecin Production by in Vitro Cultures of Ophiorrhiza liukiuensis and O. kuroiwai
    Plant Biotechnology (2004)
    Takashi AsanoIkumi WataseHiroshi SudoMariko KitajimaHiromitsu Takayama
    Camptothecin-derived compounds are widely used for clinical treatment of human cancer. They are synthesized from natural camptothecin, which is obtained by extraction from intact plants. For the feasible production of camptothecin, tissue cultures of Ophiorrhiza liukiuensis and O. kuroiwai, an interspecies hybrid of O. liukiuensis and O. pumila, have been investigated. The aseptic plants and hairy roots of O. liukiuensis and O. kuroiwai were established in addition to the previously-established O. pumila. The camptothecin production by O. kuroiwai was better than that by O. liukiuensis. 10-Methoxycamptothecin was accumulated in tissue cultures of O. liukiuensis and O. kuroiwai but not in O. pumila. Methyl jasmonic acid slightly enhanced the production of camptothecin in the O. liukiuensis hairy roots. These results indicate that the tissue cultures of O. liukiuensis and O. kuroiwai would be the feasible ways for production of camptothecin and related alkaloids.
    Camptothecin
    Jasmonic acid
    Citations (47)
    [Effects of cu2+ on biosynthesis of camptothecin in cell cultures of Camptotheca acuminata].
    Qing GuDafeng SongHong ZhangZhu Mu-yuan
    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 Cu~(2+) on camptothecin accumulation in Camptotheca acuminata cell line was described in this paper. The results showed that the optimum CuCl-2 concentration in B5 medium was 0.008mg/mL, which increased camptothecin production for 30 times compare to the control while has no inhibitive effects on cell growth, at the same time, the peroxidase activity was increased and the anthocyanidin accumulation was inhibited. The promotive effects of Cu~(2+) on camptothecin accumulation in light was higher than that in dark.
    Camptothecin
    Citations (5)
    Research progress on the biosynthesis and metabolic engineering of the anti-cancer drug camptothecin in Camptotheca acuminate
    Industrial Crops and Products (2022)
    Xiaoxuan FanXinting LinQingyan RuanJingyi WangYinkai Yang
    Camptothecin
    Topotecan
    Citations (26)
    [Improved camptothecin production by cell lines of Camptotheca acuminata].
    PubMed (2003)
    Wen Zhe Liu
    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%.
    Camptothecin
    Callus
    Suspension culture
    Citations (1)
    Sites of Accumulation of the Antitumor Alkaloid Camptothecin inCamptotheca acuminata
    Planta Medica (1994)
    Melina López‐MeyerCraig L. NesslerThomas D. McKnight
    Camptothecin is an anticancer and antiviral 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 concentration and absolute amount of camptothecin decreases rapidly. The high levels of camptothecin in young leaves could provide an easily harvested, non-destructive source of this important drug.
    Camptothecin
    Citations (100)
    Novel C-ring analogues of 20( S )-camptothecin. Part 3: synthesis and their in vitro cytotoxicity of A-, B- and C-ring analogues
    Bioorganic & Medicinal Chemistry Letters (2000)
    Duvvuri SubrahmanyamVedula M. SarmaVenkateswarlu AkellaThungathurthi V. R. S. SastryAkella S. S. V. Srinivas
    Camptothecin
    Structure–activity relationship
    Citations (24)
    Camptothecin accumulation in Camptotheca acuminata seedlings in response to acetylsalicylic acid treatment
    Canadian Journal of Plant Science (2004)
    Zhanhai LiZhijun Liu
    Camptothecin is an anti-cancer alkaloid. Acetylsalicylic acid (ASA) treatment was evaluated as a potential tool for increasing camptothecin accumulation (concentration and yield) in Camptotheca acuminata. Increasing ASA concentration increased leaf camptothecin concentration, but stunted growth and decreased total leaf camptothecin yield. Thus, ASA treatment does not enhance camptothecin yield. Key words: Hydroponic culture, plant secondary metabolite
    Camptothecin
    Citations (4)
    Camptothecin Production by In Vitro Cultures and Plant Regeneration in Ophiorrhiza Species
    Methods in molecular biology (2009)
    Takashi AsanoHiroshi SudoMami YamazakiKazuki Saito
    Camptothecin
    Citations (21)
    Camptothecin overcomes MDR1-mediated resistance in human KB carcinoma cells.
    PubMed (1991)
    A Y ChenChiang YuM PotmĕsilMonroe E. WallM. C. Wani
    In order to understand the high efficacy of camptothecin derivatives against human colon tumor xenografts in nude mice, we have studied the transport properties of camptothecin derivatives across cellular membranes of MDR1-overexpressing cells. MDR1 overexpression was shown to have little effect on camptothecin cytotoxicity; camptothecin was equally cytotoxic to both the drug-sensitive parental cell line, KB 3-1, and its multidrug-resistant derivative, KB V1. The ability of camptothecin to overcome MDR1-mediated resistance is most likely due to unimpaired accumulation of camptothecin in MDR1 cells as suggested from the following experiments: (a) cytotoxicity of camptothecin against KB V1 cells was not altered by the known MDR1-reversing agent, verapamil; (b) camptothecin was ineffective as compared with vinblastine in competing with [3H]azidopine for photoaffinity labeling of MDR1; (c) camptothecin was equally efficient in trapping cellular topoisomerase I molecules on chromosomal DNA in the form of cleavable complexes in both KB 3-1 and KB V1 cells. The mechanism by which camptothecin overcomes MDR1-mediated resistance has been further studied using a number of uncharged and charged camptothecin derivatives. In contrast to the uncharged camptothecin derivatives, such as 9-amino-camptothecin and 10,11-methylenedioxy-camptothecin, the charged camptothecin derivative, topotecan, showed reduced cytotoxicity against MDR1-overexpressing KB V1 cells. The reduced cytotoxicity of topotecan in KB V1 cells was due to the overexpression of MDR1 in KB V1 cells since verapamil restored both topotecan accumulation and cytotoxicity. These results suggest that the charge on camptothecin can affect the drug's sensitivity to MDR1. The possible effect of membrane permeability in determining drug selectivity of MDR1 is discussed.
    Camptothecin
    Topotecan
    Citations (159)
    Biosynthetic system of camptothecin: An anticancer plant product
    Pure and Applied Chemistry (2010)
    Mami YamazakiTakashi AsanoYasuyo YamazakiSupaart SirikantaramasHiroshi Sudo
    Camptothecin is one of the clinically used anticancer compounds derived from plants. We have established a hairy root culture Ophiorrhiza pumila , which efficiently produces camptothecin. The strictosidine synthase cDNA was obtained from O. pumila , and its properties were characterized using recombinant protein expressed in Escherichia coli . The mechanisms of camptothecin transport and self-resistance of producing plant cells have also been investigated. These studies offer a basis for pathway engineering of camptothecin in the future.
    Camptothecin
    Citations (22)