Evaluation of genotoxic and anti-mutagenic properties of cleistanthin A and cleistanthoside a tetraacetate

Abstract

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 andanti-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 bothmetabolic 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.