Title:Cytostatic and Apoptotic Effects of DNMT and HDAC Inhibitors in Endometrial Cancer Cells
Volume: 20
Issue: 11
Author(s): Shaohua Xu, Juan Ren, Hai Bin Chen, Yanlin Wang, Qingyou Liu, Run Zhang, Shi-Wen Jiang and Jinping Li
Affiliation:
Keywords:
HDAC inhibitor, DNMT inhibitor, endometrial cancer, cell cycle, apoptosis.
Abstract: DNA methyltransferase (DNMT) and histone deacetylase are key enzymes mediating the epigenetic regulation of gene expression.
DNA hypermethylation and/or histone deacetylation in promoter regions is often associated with downregulation or silencing of
transcription. Epigenetic silencing of tumor suppressor genes plays an important role in malignant transformation. DNMT and HDAC inhibitors
induce DNA demethylation and histone acetylation, respectively, leading to reactivation of silenced genes, and dramatic morphological
and functional changes in cancer cells. In this study, we have conducted a series of experiments to characterize the effects of epigenetic
inhibitors in endometrial cancer cells. Using cell lines representing different stages of endometrioid cancers, we examined the
impact of DNMT inhibitor, ADC, and HDAC inhibitor, TSA, on cell cycle and apoptosis. We found that while both reagents were capable
of inhibiting cell proliferation and inducing cell apoptosis, TSA appeared to be a more potent apoptosis inducer, but with a smaller effect
on cell cycle. On the other hand, ADC exhibited strong effects on cell cycle regulation, but had smaller impact on cell apoptosis. We
subsequently confirmed the presence of a strong synergism between DNMT and HDAC inhibitors. Thus, ADC and TSA exhibited strong
cytostatic and apoptotic effects in endometrial cancer cell lines and the combined application may deliver the highest response in the
clinical setting.
