Your browser doesn't support javascript.
loading
Quercetin modifies 5'CpG promoter methylation and reactivates various tumor suppressor genes by modulating epigenetic marks in human cervical cancer cells.
Kedhari Sundaram, Madhumitha; Hussain, Arif; Haque, Shafiul; Raina, Ritu; Afroze, Nazia.
Afiliação
  • Kedhari Sundaram M; School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates.
  • Hussain A; School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates.
  • Haque S; Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.
  • Raina R; School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates.
  • Afroze N; School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates.
J Cell Biochem ; 120(10): 18357-18369, 2019 10.
Article em En | MEDLINE | ID: mdl-31172592
ABSTRACT
The central role of epigenomic alterations in carcinogenesis has been widely acknowledged, particularly the impact of DNA methylation on gene expression across all stages of carcinogenesis is considered vital for both diagnostic and therapeutic strategies. Dietary phytochemicals hold great promise as safe anticancer agents and effective epigenetic modulators. This study was designed to investigate the potential of a phytochemical, quercetin as a modulator of the epigenetic pathways for anticancer strategies. Biochemical activity of DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and global genomic DNA methylation was quantitated by an enzyme-linked immunosorbent assay based assay in quercetin-treated HeLa cells. Molecular docking studies were performed to predict the interaction of quercetin with DNMTs and HDACs. Quantitative methylation array was used to assess quercetin-mediated alterations in the promoter methylation of selected tumor suppressor genes (TSGs). Quercetin induced modulation of chromatin modifiers including DNMTs, HDACs, histone acetyltransferases (HAT) and HMTs, and TSGs were assessed by quantitative reverse transcription PCR (qRT-PCR). It was found that quercetin modulates the expression of various chromatin modifiers and decreases the activity of DNMTs, HDACs, and HMTs in a dose-dependent manner. Molecular docking results suggest that quercetin could function as a competitive inhibitor by interacting with residues in the catalytic cavity of several DNMTs and HDACs. Quercetin downregulated global DNA methylation levels in a dose- and time-dependent manner. The tested TSGs showed steep dose-dependent decline in promoter methylation with the restoration of their expression. Our study provides an understanding of the quercetin's mechanism of action and will aid in its development as a candidate for epigenetic-based anticancer therapy.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quercetina / Neoplasias do Colo do Útero / Epigênese Genética Limite: Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quercetina / Neoplasias do Colo do Útero / Epigênese Genética Limite: Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article