Inhibition of cell growth and potentiation of tumor necrosis factor-α (TNF-α)-induced apoptosis by a phenanthroindolizidine alkaloid antofine in human colon cancer cells

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• 作者：Hye-Young Min ; Hwa-Jin Chung ; Eun-Hye Kim ; Sanghee Kim ; Eun-Jung Park ; Sang Kook Lee
• 关键词：Antofine ; Phenanthroindolizidine alkaloid ; Anti-proliferation ; Antitumor
• 刊名：Biochemical Pharmacology
• 出版年：2010
• 出版时间：1 November 2010
• 年：2010
• 卷：80
• 期：9
• 页码：1356-1364
• 全文大小：474 K

文摘

Based on the potential of natural products as a source for the development of cancer chemotherapeutic agents, this study was performed to investigate the anti-proliferative and antitumor effects of antofine, a phenanthroindolizidine alkaloid derived from Cynanchum paniculatum. Antofine showed potent anti-proliferative effects in several human cancer cells with IC₅₀ values in the nanomolar range. Treatment with antofine for 24 h did not result in the induction of apoptotic cell death but moderately induced cell cycle arrest at G0/G1 phase and inhibited the expression of cyclin D1, cyclin E, and CDK4. In addition, antofine inhibited the transcriptional activity of β-catenin/Tcf in human colon HCT 116 cells, and the expression level of β-catenin and cyclin D1 was also down-regulated by antofine in human colon SW480 cells. Moreover, antofine potentiated tumor necrosis factor-α (TNF-α)-induced apoptosis, which was demonstrated by the increase of Annexin V-positive cell population and of the cleavage of poly (ADP-ribose) polymerase (PARP) and caspase-8. Antofine also effectively suppressed tumor growth in the HCT 116 implanted xenograft nude mouse model. Taken together, these findings suggest that antofine might be a potential candidate for the development of cancer chemotherapeutic agents derived from natural products.