Cytotoxic and Antineoplastic Activity of Timosaponin A-III for Human Colon Cancer Cells

초록

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 GO/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 Week's 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.

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