Genistein induces activation of the mitochondrial apoptosis pathway by inhibiting phosphorylation of Akt in colorectal cancer cells |
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Authors: | Jian Qin JiaAn Teng Zhou Zhu JiaXin Chen |
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Institution: | 1. Department of Radiation Oncology of Clinical Cancer Center,;2. Department of Cadre Medicine, Division of Endocrinology and Metabolism and;3. Department of Gastrointestinal and Peripheral Vascular Surgery, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China, and |
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Abstract: | Context: Genistein inhibits the proliferation and induces apoptosis of colorectal cancer cells; however, the underling molecular mechanisms remain to be determined.Aim: The aim of this study was to investigate whether genistein reduces cell viability by suppressing the phosphorylation of AKT and activating the mitochondrial apoptosis pathway in colorectal cancer cells.Materials and methods: The anti-proliferative effects of genistein (0, 25, 50, and 100?μM) on HCT-116 and LoVo cells were assessed using MTT assay. Genistein-induced apoptosis was measured by Hoechst 33258 staining and flow cytometry. The mRNA level of Bax was detected by real-time PCR. The protein levels of Bax, total Akt, and phosphorylated Akt were assessed by western blot.Results: The IC50 values of genistein were 690, 135, and 61?μM in HCT-116 cells and 204, 135, and 93?μM in LoVo cells after treatment for 24, 48, and 72?h, respectively. After treatment with different concentrations of genistein (0, 25, 50, and 100?μM) for 48?h, the early apoptotic cells in HCT-116 increased from 1.99%?±?0.55% to 6.78%?±?2.12%, 23.16%?±?3.87%, and 36.99%?±?3.76%, respectively. The same concentrations of genistein increased the early apoptotic cells in LoVo from 2.56%?±?1.42% to 3.21%?±?1.52%, 18.22%?±?3.56%, and 23.56%?±?3.02%, respectively. Moreover, genistein increased the mRNA and protein levels of Bax, while it inhibited the phosphorylation of Akt in HCT-116 cells.Conclusion: Genistein inhibited cell proliferation and induced apoptosis of colorectal cancer cells. Genistein induced the mitochondrial pathway of apoptosis in HCT-116 cells by inhibiting phosphorylation of Akt. |
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Keywords: | Akt apoptosis bax colorectal cancer cell genistein HCT-116 LoVo |
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