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Effect of Histone Deacetylase Inhibitors on Vitamin D Dependent Gene Expression in Human Colorectal and Breast Cancers
Author(s) -
Hossain Sharmin
Publication year - 2017
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.31.1_supplement.644.7
Subject(s) - sulforaphane , dkk1 , histone deacetylase , calcitriol receptor , chemistry , acetylation , vitamin d and neurology , cancer research , vitamin , endocrinology , medicine , pharmacology , histone , wnt signaling pathway , biology , biochemistry , signal transduction , gene
There are little evidence on the effect of histone deacetylation by a specific histone deacetylase inhibitor (HDACI), sulforaphane, on vitamin D dependent genes in human colorectal and breast cancers. Sulforaphane is a bioactive compound present in cruciferous vegetables like broccoli, Brussel sprouts etc. In the present study, we examined the influence of sulforaphane on expressions of vitamin D dependent genes, VDR and TRPV6, via inhibition of histone deacetylation with TSA as a positive control. We also examined DKK1, one of the inhibitors of Wnt signaling pathway, to see any potential effect of Vitamin D, sulforaphane (SFN) and/or the combination treatment on its regulation. The effects of SFN and TSA with and without the presence of vitamin D were tested on Caco‐2 and TMX2–28 (breast cancer) cells. Although not statistically significant, we found vitamin D to increase the expressions of VDR (2.3 fold) and TRPV6 (2.8 fold) compared to control. The expression of TRPV6 was increased two‐fold by the combination of vitamin D+TSA and three‐fold by TSA alone. DKK1 expression was increased upon treatment with vitamin D+TSA (fold increase 2.8) and TSA alone (fold increase 3.4). DKK1 expression was also increased by SFN (2.7 fold) suggesting a stand‐alone effect. Expression of DKK1 was also increased in TMX2–28 cells upon treatment with sulforaphane (1.5 fold) and the combination of vitamin D + sulforaphane (1.4 fold). Vitamin D (alone or in combination) with sulforaphane can be an effective nutrigenomic intervention for colorectal and/or breast cancer through the inhibition of histone deacetylation‐ a crucial epigenetic modification process. This research, therefore, has the potential to create a prospective model for epigenetic control in cancer. Support or Funding Information Hatch Grant# MAS00992