Effect of SAHA on the Expression of Chromatin Modifying Enzymes in Prostate and Breast Cancer Cells

Nova Southeastern University, Davie, Florida, USA

Objective. Our study analyzed the effects of HDAC inhibitor SAHA treatment on gene expressions of Chromatin Modifying Enzymes. Background. Histone deacetylase (HDAC) inhibitors are one of the important epigenetic regulators that have enormous therapeutic potential in various diseases, including cancers. For example, SAHA (Suberoylanilidehydroxamic acid) has been known as a potent inhibitor of histone deacetylases that eventually lead to differentiation, growth arrest, and apoptosis of various cancer cells. Methods. In our study, we utilized the RT2 Profiler PCR Array that was specific for the Human Epigenetic Chromatin Modifying Enzymes. We examined the impact of SAHA (7.5 µM) treatment on gene expression patterns of LNCaP (prostate cancer cells) and MCF-7 (breast cancer) cells. Results. As a result of SAHA treatment, the expression levels of AURKB (0.11), SUV39H1 (0.23), AURKA (0.4), and SETD7 (0.49) were found to be significantly down-regulated compared to the control in the LNCaP cells. In addition, the mRNA level of KDM6B was also up-regulated (by 2.4 folds) after SAHA treatment. On the other hand, in the MCF-7 cells PAK1 (0.06), NSD1 (0.19), SETD7 (0.24), DNMT3A (0.31), NEK6 (0.34), SETD6 (0.38), PRMT1 (0.4), AURKB (0.4) and SUV39H1 (0.45) were found to be significantly down-regulated after 24 hr of SAHA treatment. Conclusion. Our results offer evidence that SAHA can impact the gene expression profile of epigenetic chromatin modification enzymes and exert its anti-cancer effect in both prostate and breast cancer cells. Grants. The financial support from the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida is gratefully acknowledged.