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

Content Provider	Europe PMC
Author	ZHANG, ZHIYU WANG, CHONG-ZHI DU, GUANG-JIAN QI, LIAN-WEN CALWAY, TYLER HE, TONG-CHUAN DU, WEI YUAN, CHUN-SU
Copyright Year	2013
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.
ISSN	10196439
Journal	International Journal of Oncology
Volume Number	43
PubMed Central reference number	PMC3742162
Issue Number	1
PubMed reference number	23686257
e-ISSN	17912423
DOI	10.3892/ijo.2013.1946
Language	English
Publisher	D.A. Spandidos
Publisher Date	2013-05-17
Access Restriction	Open
Rights License	This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. Copyright © 2013, Spandidos Publications
Subject Keyword	colon cancer cancer chemoprevention G2/M cell cycle arrest isoflavones p53
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology