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Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells
- Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells
- Kang Y.-J.; Chung H.-J.; Nam J.-W.; Park H.J.; Seo E.K.; Kim Y.S.; Lee D.; Lee S.K.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Journal of Natural Products
- vol. 74, no. 4, pp. 701 - 706
- SCI; SCIE; SCOPUS
- 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. © 2011 The American Chemical Society and American Society of Pharmacognosy.
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