Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells

The potential antitumor activity of timosaponin A-III (1), a steroidal saponin from the rhizomes of Anemarrhena asphodeloides, was investigated in human colorectal Cancer HCT-15 cells both in Cell Culture and in an in vivo murine xenograft model. Compound 1 inhibited the proliferation of Cancer cells with cell-cycle arrest and induction of Apoptosis. Cell-cycle arrest in the G0/G1 and G2/M phase by 1 was correlated with the down-regulation of cyclin A, cyclin B1, cyclin-dependent kinase 2 (CDK2), CDK4, proliferating cell nuclear antigen, and c-Myc. The increase of the sub-G1 peak by 1 was also closely related to the induction of Apoptosis, which was evidenced by the induction of DNA fragmentation, activation of caspases, induction of cleaved poly-(ADP ribose) polymerase, and suppression of Bcl-xL and Bcl-2 expression. In an in vivo xenograft model, treatment with 1 (2 or 5 mg/kg body weight, three times/week, IP administration) for four weeks significantly suppressed tumor growth in athymic nude mice bearing HCT-15 cells, without any overt toxicity. Cell-cycle arrest and induction of Apoptosis might be plausible mechanisms of actions for the observed antineoplastic activity of 1.