Himakoun Lakana, Tuchinda Patoomratana, Puchadapirom Pranom, Tammasakchai Ratigon, Leardkamolkarn Vijittra
Department of Pathobiology, Mahidol University, Bangkok, Thailand.
Asian Pac J Cancer Prev. 2011;12(12):3271-5.
Cleistanthin A (CleinA) and cleistanthoside A (CleisA) isolated from plant Phyllanthus taxodiifolius Beille have previously shown potent anticancer effects. To promote their medicinal benefits, CleisA was modified to cleistanthoside A tetraacetate (CleisTA) and evaluated for genotoxic and anti-mutagenic properties in comparison with CleinA. Both compounds showed no significant mutagenic activity to S. typhimulium bacteria and no cytotoxic effect to normal mammalian cells. The non genotoxic effect of CleinA was further confirmed by un-alteration of cytokinesis-block proliferation index (CBPI) and micronucleus (MN) frequency assays in Chinese hamster lung fibroblast (V79) cells, and of CleisTA was confirmed by un-changes of human peripheral blood lymphocytes (HPBL) chromosomal structure assay. Moreover, the metabolic form of CleinA efficiently demonstrated cytostasis effect to V79 cell and prevented mutagen induced Salmonella TA98 and TA100 reversion, whereas both metabolic and non-metabolic forms of CleisTA reduced HPBL mitotic index (%M.I) in a concentration-dependent relationship. The results support CleinA and CleisTA as the new lead compounds for anti-cancer drug development.
从植物水松叶叶下珠（Phyllanthus taxodiifolius Beille）中分离得到的叶下珠素A（CleinA）和叶下珠苷A（CleisA）此前已显示出强大的抗癌作用。为了提升它们的药用价值，将CleisA修饰为叶下珠苷A四乙酸酯（CleisTA），并与CleinA相比评估其遗传毒性和抗诱变特性。两种化合物对鼠伤寒沙门氏菌均无明显诱变活性，对正常哺乳动物细胞也无细胞毒性作用。在中华仓鼠肺成纤维细胞（V79）中，胞质分裂阻断增殖指数（CBPI）和微核（MN）频率测定未发生改变，进一步证实了CleinA的非遗传毒性作用；在人外周血淋巴细胞（HPBL）染色体结构测定中未出现变化，证实了CleisTA的非遗传毒性作用。此外，CleinA的代谢形式对V79细胞有效显示出细胞生长抑制作用，并能防止诱变剂诱导的沙门氏菌TA98和TA100回复突变，而CleisTA的代谢形式和非代谢形式均以浓度依赖关系降低HPBL有丝分裂指数（%M.I）。这些结果支持CleinA和CleisTA作为抗癌药物开发的新先导化合物。
