Premium
Genistein Affects Dickkopf‐related Protein 1 (DKK1) Expression Level through Histone Modification in SW480 Human Colon Cancer Cell Line
Author(s) -
Wang Huan,
Pan YuanXiang,
Chen Hong
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.918.4
Subject(s) - genistein , dkk1 , histone deacetylase , trichostatin a , acetylation , chemistry , histone , microbiology and biotechnology , cell cycle , chromatin immunoprecipitation , cell growth , cancer research , biology , wnt signaling pathway , signal transduction , gene expression , cell , endocrinology , biochemistry , promoter , gene
Genistein is a plant‐derived isoflavone and can block uncontrolled tumor cell growth by inhibiting cell division and survival. This study is to test the hypothesis that the anticancer effect of genistein in colon cancer is through inhibition of the WNT signaling pathway by promoting an antagonist Dkk1 of the pathway. Human cancer cell line SW480 was treated with 0, 1, 5, 15, 25, 50, and 75 μM genistein for 2 days. Flow cytometry of cell cycle analysis showed that genistein induced a concentration‐dependent G2 phase arrest in SW480. Genistein also reduced cell proliferation by WST1 assay. Both Dkk1 mRNA and protein expression are increased by genistein at higher concentrations. DNA methylation at Dkk1 promoter region in SW480 was not affected by genistein treatment. On the other hand, chromatin immunoprecipitation showed that genistein induced histone H3 acetylation at Dkk1 promoter region, which indicates that increased histone acetylation is associated with increased Dkk1 expression. Treatment with histone deacetylase inhibitor trichostatin A confirmed that increasing histone acetylation can lead to the induction of Dkk1 mRNA expression. In conclusion, genistein treatment decreases cell growth and proliferation in colon cancer cell line SW480. The effect is associated with increased Dkk1 expression through the induction of histone acetylation at the promoter region of the gene.