Genistein Induces G2/M Arrest in Gastric Cancer Cells by Increasing the Tumor Suppressor PTEN Expression |
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| Authors: | Yan-Long Liu Guo-Qiang Zhang Yue Yang Chun-Yan Zhang Rong-Xia Fu Yan-Mei Yang |
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| Institution: | 1. Department of Colorectal Surgery , the Third Affiliated Hospital of Harbin Medical University , Harbin , China;2. Department of Breast Surgery , the Third Affiliated Hospital of Harbin Medical University , Harbin , China;3. Cancer Research Institute , Harbin Medical University , Harbin , China;4. Biological Engineering Laboratory, Department of Food Science , Tianjin Agricultural University , Tianjin , China |
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| Abstract: | Genistein, a major isoflavone found in soybeans, exhibits anticarcinogenic properties. The inhibitory effect of genistein on cell proliferation is associated with G2/M cell cycle arrest and inhibition of cdc2 activities. Here we assessed the role of PTEN in regulation of genistein-mediated G2/M cell cycle arrest in the gastric cancer cell lines (SGC-7901 and BGC-823). After 24 h following treatment, genistein induced a concentration-dependent accumulation of cells in the G2/M phase of the cell cycle. The sustained G2/M arrest by genistein in SGC-7901 and BGC-823 cells is associated with increased phospho-cdc2 (Tyr15) and decreased cdc2 protein. Genistein treatment increased Wee1 levels and decreased phospho-Wee1 (Ser 642). Moreover, genistein substantially decreased the Ser473 and Thr308 phosphorylation of Akt and upregulated PTEN expression. Downregulation of PTEN by siRNA in genistein-treated cells increased phospho-Wee1 (Ser642), whereas decreased phospho-Cdc2 (Tyr15), resulting in decreased the G2/M cell cycle arrest. Therefore, induction of G2/M cell cycle arrest by genistein involved upregulation of PTEN. |
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