ABSTRACT
Maspin repression is frequently observed in prostate cancer; however, the molecular mechanism(s) causing the loss is not completely understood. Here, we demonstrate that inhibition of class I histone deacetylases (HDACs) mediates re-expression of maspin which plays an essential role in suppressing proliferation and migration capability in prostate cancer cells. Human prostate cancer LNCaP and DU145 cells treated with HDAC inhibitors, sodium butyrate, and trichostatin A, resulted in maspin re-expression. Interestingly, an exploration into the molecular mechanisms demonstrates that maspin repression in prostate tumor and human prostate cancer cell lines occurs via epigenetic silencing through an increase in HDAC activity/expression, independent of promoter DNA hypermethylation. Furthermore, transcriptional activation of maspin was accompanied with the suppression of HDAC1 and HDAC8 with significant p53 enrichment at the maspin promoter associated with an increase in histone H3/H4 acetylation. Our results provide evidence of maspin induction as a critical epigenetic event altered by class I HDACs in the restoration of balance to delay proliferation and migration ability of prostate cancer cells.
Subject(s)
Biomarkers, Tumor/metabolism , DNA Methylation , Gene Expression Regulation, Neoplastic , Histone Deacetylases/metabolism , Prostatic Neoplasms/pathology , Serpins/genetics , Apoptosis , Biomarkers, Tumor/genetics , Cell Proliferation , Epigenesis, Genetic , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylases/chemistry , Histone Deacetylases/genetics , Histones , Humans , Hydroxamic Acids/pharmacology , Male , Prognosis , Promoter Regions, Genetic , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Serpins/metabolism , Tumor Cells, CulturedABSTRACT
The influence of diet and environment on human health has been known since ages. Plant-derived natural bioactive compounds (phytochemicals) have acquired an important role in human diet as potent antioxidants and cancer chemopreventive agents. In past few decades, the role of epigenetic alterations such as DNA methylation, histone modifications and non-coding RNAs in the regulation of mammalian genome have been comprehensively addressed. Although the effects of dietary phytochemicals on gene expression and signaling pathways have been widely studied in cancer, the impact of these dietary compounds on mammalian epigenome is rapidly emerging. The present review outlines the role of different epigenetic mechanisms in the regulation and maintenance of mammalian genome and focuses on the role of dietary phytochemicals as epigenetic modifiers in cancer. Above all, the review focuses on summarizing the progress made thus far in cancer chemoprevention with dietary phytochemicals, the heightened interest and challenges in the future.