Abstract
Genistein, a soy‐derived isoflavone, has been shown to suppress colon cancer progression by regulating different cellular properties. The aim of the study is to investigate the role of Activating Transcription Factor 3 (ATF3), an immediate‐early response gene, in genistein‐modulated cell cycle arrest and apoptosis in a human colon cancer cell line SW620. Results showed that genistein induced G2 phase arrest and increased late apoptosis in SW620. Genistein also increased the expression of ATF3 mRNA and protein, as well as its transcriptional activity in SW620. mRNA expression of downstream genes of ATF3, such as cell cycle inhibitors p53, p21, CyclinD1, and apoptotic enzymes Casp8, and Casp9, were all induced by genistein. Chromatin immunoprecipitation (ChIP) showed decreased phosphorylated histone H3 serine 10 (H3S10p) at both the promoter and coding region of ATF3. In addition, genistein increased trimethylated histone H3 lysine 36 (H3K36me3) level at a coding region and dimethylated histone H3 lysine 4 (H3K4me2) level at the promoter region. Methylation sensitive PCR showed that genistein did not change the level of DNA methylation at various regions of ATF3 gene. In conclusion, genistein‐mediated histone modifications of ATF3 may lead to G2 phase arrest and apoptosis in SW620.
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