Abstract 4681: Effect of SAHA on epigenetic chromatin modification enzymes in LNCaP and MCF-7 cells

Abstract

Abstract Several epigenetic modifications of histones are associated with the pathogenesis of various diseases including cancers. Histone modifications are one of the key epigenetic regulators that control chromatin structure and gene transcription, thereby impacting various important cellular functions and causing variations in phenotypes. Histone modifications can contribute to chromatin compaction, alterations in gene transcription and modifications in nucleosome dynamics. The epigenetic changes could be implemented in response to intrinsic and external stimuli. Moreover, the dysregulation of the epigenetic balance can change the patterns of gene expression leading to either gain or loss of cell cycle control. 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. Histone modifying enzymes such as HDAC and HAT (Histone Acetyltransferaases) and DMT (DNA Methyl Transferases) catalyze the addition or removal methyl or acetyl groups through covalent modifications in DNA histone and-non histone proteins. These modifications eventually regulate gene expression as well as other genomic functions that contribute to the maintenance of cell identity and their fate. In addition to influencing gene expression, HDAC enzymes also regulate many nonhistone targets by altering their function at the cellular and systemic levels. In our present study, RT2 Profiler PCR Array for the Human Epigenetic Chromatin Modification Enzymes was used to examine the impact of SAHA (7.5 µM) treatment on gene expression patterns of LNCaP (prostate cancer cells) and MCF-7 (breast cancer) cells. As a result of SAHA treatment, in the LNCaP cells, 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. Besides, the mRNA level of KDM6B was 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 SAHA treatment for 24 hrs. Our results offer evidence that SAHA can impact the gene expressions of epigenetic chromatin modification enzymes and exert the anti-cancer effect in both prostate and breast cancer cells. Further studies are needed to fully understand the similarities and disparities in the gene expression profiles (GEP) of these cells following the inhibition of HDACS using SAHA (The financial support from the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida is gratefully acknowledged). Citation Format: Thiagarajan Venkatesan, Umamaheswari Natarajan, Appu Rathinavelu. Effect of SAHA on epigenetic chromatin modification enzymes in LNCaP and MCF-7 cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4681.