Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells

  • Authors:
    • Zhiyu Zhang
    • Chong-Zhi Wang
    • Guang-Jian Du
    • Lian-Wen Qi
    • Tyler Calway
    • Tong-Chuan He
    • Wei Du
    • Chun-Su Yuan
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  • Published online on: May 17, 2013     https://doi.org/10.3892/ijo.2013.1946
  • Pages: 289-296
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Abstract

Soybean isoflavones have been used as a potential preventive agent in anticancer research for many years. Genistein is one of the most active flavonoids in soybeans. Accumulating evidence suggests that genistein alters a variety of biological processes in estrogen-related malignancies, such as breast and prostate cancers. However, the molecular mechanism of genistein in the prevention of human colon cancer remains unclear. Here we attempted to elucidate the anticarcinogenic mechanism of genistein in human colon cancer cells. First we evaluated the growth inhibitory effect of genistein and two other isoflavones, daidzein and biochanin A, on HCT-116 and SW-480 human colon cancer cells. In addition, flow cyto­metry was performed to observe the morphological changes in HCT-116/SW-480 cells undergoing apoptosis or cell cycle arrest, which had been visualized using Annexin V-FITC and/or propidium iodide staining. Real-time PCR and western blot analyses were also employed to study the changes in expression of several important genes associated with cell cycle regulation. Our data showed that genistein, daidzein and biochanin A exhibited growth inhibitory effects on HCT-116/SW-480 colon cancer cells and promoted apoptosis. Genistein showed a significantly greater effect than the other two compounds, in a time- and dose-dependent manner. In addition, genistein caused cell cycle arrest in the G2/M phase, which was accompanied by activation of ATM/p53, p21waf1/cip1 and GADD45α as well as downregulation of cdc2 and cdc25A demonstrated by q-PCR and immunoblotting assay. Interestingly, genistein induced G2/M cell cycle arrest in a p53-dependent manner. These findings exemplify that isoflavones, especially genistein, could promote colon cancer cell growth inhibition and facilitate apoptosis and cell cycle arrest in the G2/M phase. The ATM/p53-p21 cross-regulatory network may play a crucial role in mediating the anticarcinogenic activities of genistein in colon cancer.
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July 2013
Volume 43 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Zhang Z, Wang C, Du G, Qi L, Calway T, He T, Du W and Yuan C: Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells. Int J Oncol 43: 289-296, 2013
APA
Zhang, Z., Wang, C., Du, G., Qi, L., Calway, T., He, T. ... Yuan, C. (2013). Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells. International Journal of Oncology, 43, 289-296. https://doi.org/10.3892/ijo.2013.1946
MLA
Zhang, Z., Wang, C., Du, G., Qi, L., Calway, T., He, T., Du, W., Yuan, C."Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells". International Journal of Oncology 43.1 (2013): 289-296.
Chicago
Zhang, Z., Wang, C., Du, G., Qi, L., Calway, T., He, T., Du, W., Yuan, C."Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells". International Journal of Oncology 43, no. 1 (2013): 289-296. https://doi.org/10.3892/ijo.2013.1946