Genistein induces gadd45 gene and G2/M cell cycle arrest in the DU145 human prostate cancer cell line

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Genistein is the most abundant isoflavone of soybeans, and has been shown to cause growth arrest in various human cancer cell lines. However, the precise mechanism for this is still unclear. We present that the gadd45 gene is induced by genistein via its promoter in a DU145 human prostate cancer cell line. In this study, we found that the genistein-responsive element of gadd45 promoter was the CCAAT site. Others and we have previously reported that the Oct-1 and the CCAAT sites of the promoter region are important for induction of the gadd45 gene. The results of EMSA suggest that this induction of gadd45 by genistein is caused by the increased binding of NF-Y to the CCAAT site of the promoter region. On the other hand, genistein did not increase the amount of NF-Y protein in DU145 cells. The Gadd45 protein is reported to have roles in cell cycle regulation, apoptosis, and genomic stability. Therefore, finding agents that transcriptionally upregulate this gene in cancer cells may contribute to new strategies for the prevention or therapy for cancer, which we have termed ‘gene-regulating chemoprevention or chemotherapy’. In this sense, genistein, which activates gadd45 gene expression, would represent a gene-regulating chemopreventive agent.