Resveratrol up-regulates ATP2A3 gene expression in breast cancer cell lines through epigenetic mechanisms.

Resveratrol up-regulates ATP2A3 gene expression in breast cancer cell lines through epigenetic mechanisms. Int J Biochem Cell Biol. 2019 Jun 04;: Authors: Izquierdo-Torres E, Hernández-Oliveras A, Meneses-Morales I, Rodríguez G, Fuentes-García G, Zarain-Herzberg Á Abstract Resveratrol (RSV) is a phytoestrogen which has been related to chemoprevention of several types of cancer. In this work, we show up to a 6-fold increased expression of ATP2A3 gene induced by RSV that triggers apoptosis and changes of intracellular Ca2+ management in MCF-7 and MDA-MB-231 breast cancer cell lines. We explored epigenetic mechanisms for that RSV-induced ATP2A3 up-regulation. The results indicate that RSV-induced ATP2A3 up-regulation correlates with about 50% of reduced HDAC activity and reduced nuclear HDAC2 expression and occupancy on ATP2A3 promoter, increasing the global acetylation of histone H3 and the enrichment of histone mark H3K27Ac on the proximal promoter of the ATP2A3 gene in MDA-MB-231 cells. We also quantified HAT activity, finding that it can be boosted with RSV treatment; however, pharmacological inhibition of p300, one of the main HATs, did not have significant effects in RSV-mediated ATP2A3 gene expression. Additionally, DNMT activity was also reduced in cells treated with RSV, as well as the expression of Methyl-DNA binding proteins MeCP2 and MBD2. However, analysis of the methylation pattern of ATP2A3 gene promoter showed un-met...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research