Induction of Apoptosis by Rhinacanthone Isolated from Rhinacanthus nasutus Roots in Human Cervical Carcinoma Cells
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概要
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Rhinacanthone, a main bioactive naphthoquinone, isolated from roots of Rhinacanthus nasutus KURZ, (family Acanthaceae), a Thai traditional medicine, has been reported to possess anticancer effects, although the anticancer mechanism is still unclear. Therefore, we investigated the effects of rhinacanthone on cell proliferation, cell cycle progression and apoptosis induction in human cervical carcinoma (HeLa) cells. β-Lapachone, an anticancer drug having a chemical structure related to rhinacanthone, was used as a positive control. The results demonstrated that rhinacanthone inhibited proliferation of HeLa cells in a dose-dependent manner and had greater efficacy than that of β-lapachone: IC50 values of the compound ranged from 1.2±0.1 to 5.5±0.86 μM for 2—24 h time periods. Rhinacanthone-treated HeLa cells displayed several apoptotic features as evidenced by the appearance of chromatin condensation, internucleosomal DNA fragmentation, increase in the proportion of sub G1 apoptotic cells, and externalization of annexin-V. The apoptotic processes by the treatment with rhinacanthone involved in a marked increase in the level of pro-apoptotic protein Bax and decrease in the levels of anti-apoptotic proteins Bcl-2 and survivin as well as subsequent activation of caspase-9 and caspase-3. Moreover, rhinacanthone increased the expression of apoptosis-inducing factor (AIF) which would translocate from mitochondria to nucleus through cytosol, and induce apoptosis through caspase independent signaling pathway. Taken together, our findings for the first time demonstrate that rhinacanthone-induced apoptosis in HeLa cells is mediated primarily through the mitochondria-dependent signaling pathway, suggesting that it may be a promising agent for the treatment of human cervical cancer.
著者
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Oku Naoto
Department Of Medical Biochemistry And Coe Program In The 21st Century University Of Shizuoka School
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Ruchirawat Somsak
Laboratory Of Medicinal Chemistry Chulabhorn Research Institute
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Yahuafai Jantana
Natural Products Research Section Research Division National Cancer Institute
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Siripong Pongpun
Res. Div. National Cancer Inst. Thailand
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Siripong Pongpun
Natural Product Research Section Research Division National Cancer Institute
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Hahnvajanawong Chariya
Faculty of Medicine, Khon Kaen University
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Piyaviriyakul Suratsawadee
Natural Products Research Section, Research Division, National Cancer Institute
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Kanokmedhakul Kwanjai
Faculty of Science, Khon Kaen University
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Kongkathip Ngampong
Faculty of Science, Kasetsart University
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OKU Naoto
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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