Association between histone deacetylase activity and vitamin D‐dependent gene expressions in relation to sulforaphane in human colorectal cancer cells

BACKGROUND It is relatively unknown as to how dietary bioactive compound sulforaphane (SFN) and vitamin D regulate gene expression in colorectal cancer. We hypothesized that a combination of SFN with vitamin D would prove beneficial in colorectal cancer. A combinatorial chemo‐preventive strategy was employed to investigate the impact of SFN on chromatin remodeling in colorectal carcinoma. To understand the epigenetics‐mediated changes in gene expression in response to SFN and vitamin D, Caco‐2 cells were exposed for 24 h to vitamin D (100 nmol L−1) either alone or in combination with SFN and trichostatin A (20 and 1 μmol L−1, respectively) at 70% confluency (proliferating) and after 13 days post‐confluency (fully differentiated). Changes to VDR, CYP24A1, CYP27B1 and TRPV6 gene expressions were quantified using real‐time PCR‐based assays. Histone deacetylase (HDAC) inhibitor activity was assessed using HDAC I/II assay that measured global changes in acetylation status. RESULTS In differentiated Caco‐2 cells, none of the genes had significant changes from D alone group. D + SFN (P = 0.99) demonstrated an opposing effect from D alone and decreased VDR expression. However, in proliferating Caco‐2 cells, D + SFN (P