Geranyl Derivative of Phloroacetophenone Induces Cancer Cell-Specific Apoptosis through Bax-Mediated Mitochondrial Pathway in MCF-7 Human Breast Cancer Cells

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概要

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• Plant-derived polyhenols inhibit cancer cell proliferation and induce apoptosis. Recently, prenylflavonoids and alkyl-phloroacetophenones have been reported for their in vitro antitumor activity. In the present study, we examined the cytotoxic activity of prenyl (3-PAP) and geranyl (3-GAP) derivatives of phloroacetophenone, and xanthohumol (XN), a prenyl-chalcone, in human breast cancer (MCF-7) and human sarcoma (HT1080) cell lines in vitro. 3-GAP showed the strongest cytotoxicity in these cell lines with IC50 values of less than 10 µM. In addition, we report that 3-GAP is a more potent anti-cancer agent for breast cancer than XN which is a well-known anticancer flavonoid. Moreover, 3-GAP did not induce cytotoxicity in the normal cell line, TCMK-1, whereas 3-PAP and XN significantly reduced TCMK-1 cell viability. In 3-GAP-treated MCF-7 cells, nuclear accumulation and transcriptional activity of p53 were increased. In addition, pro-apoptotic Bax but not B-cell lymphoma 2 (Bcl-2) expression was increased by 3-GAP. In accordance with the Bax increase, 3-GAP induced mitochondrial cytochrome c release and activated caspase-9, an initiator of the caspase cascade. In the MCF-7 cell line which does not express caspase-3, activation of caspase-7, a member of the caspase-3 subfamily, was increased by 3-GAP. The present results indicate that synthetic 3-GAP is a safe and effective anti-cancer agent, and the Bax-mediated mitochondrial pathway is the main apoptosis signaling pathway of 3-GAP in MCF-7 cells.

著者

• Kim Jung-ae

  College Of Pharmacy Yeungnam University

• PARK Su-Young

  College of Pharmacy, Yeungnam University

• Park Su-young

  College Of Pharmacy Yeungnam University

• Lee Yong

  School Of Bioscience And Biotechnology And Institute Of Bioscience And Biotechnology Kangwon Nationa

• Cho Mi-Yeon

  College of Pharmacy, Yeungnam University

• Park Sumin

  College of Pharmacy, Yeungnam University

• Han Gi-dong

  School of Food Technology and Food Service Industry, Yeungnam University

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