Pharmaceutical Biology, 2015, 54(1):74-9.

Genistein induces activation of the mitochondrial apoptosis pathway by inhibiting phosphorylation of Akt in colorectal cancer cells

Jian Qin, JiaAn Teng, Wen-Jun Huang; et al

a Department of Radiation Oncology of Clinical Cancer Center

Genistein inhibits the proliferation and induces apoptosis of colorectal cancer cells; however, the underling molecular mechanisms remain to be determined.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.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.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.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.

英国《制药生物学》

金雀异黄素通过抑制结直肠癌细胞中Akt的磷酸化来诱导线粒体凋亡途径的活化
秦建，滕家安，黄文俊，等

临床癌症中心放射肿瘤学系

金雀异黄素抑制结肠直肠癌细胞的增殖和诱导凋亡; 本研究的目的是通过抑制AKT的磷酸化和激活结直肠癌细胞的线粒体凋亡途径来研究金雀异黄素是否降低细胞活力。金雀异黄素（0，25，50和100μM）对HCT-116和LoVo细胞的抗增殖效应采用 mtt 法检测。金雀异黄素诱导的细胞凋亡通过Hoechst 33258染色和流式细胞术测量。通过实时PCR检测Bax的mRNA水平。通过蛋白质印迹评估Bax，总Akt和磷酸化Akt的蛋白质水平。在HCT-116细胞中金雀异黄素的IC 50值为690,135和61μM，在处理后的LoVo细胞中的IC 50值为204,135和93μM，检测时间为 24，48和72小时。用不同浓度的金雀异黄素（0,25,50和100μM）处理48小时后，HCT-116中的早期凋亡细胞从1.99％±0.55％增加到6.78％±2.12％，23.16％±3.87％和36.99％±3.76％。相同浓度的金雀异黄素使LoVo中的早期凋亡细胞分别从2.56％±1.42％增加到3.21％±1.52％，18.22％±3.56％和23.56％±3.02％。此外，金雀异黄素增加了Bax的mRNA和蛋白水平，同时抑制HCT-116细胞中Akt的磷酸化.Genistein抑制细胞增殖并诱导结肠直肠癌细胞的凋亡。金雀异黄素通过抑制Akt的磷酸化诱导HCT-116细胞凋亡的线粒体途径。