Abstract Title:

Genistein Modulates Signaling Pathways and Targets Several Epigenetic Markers in HeLa Cells.

Abstract Source:

Genes (Basel). 2019 Nov 21 ;10(12). Epub 2019 Nov 21. PMID: 31766427

Abstract Author(s):

Madhumitha Kedhari Sundaram, Sreepoorna Unni, Pallavi Somvanshi, Tulika Bhardwaj, Raju K Mandal, Arif Hussain, Shafiul Haque

Article Affiliation:

Madhumitha Kedhari Sundaram


BACKGROUND: Several epigenetic changes are responsible for transcriptional alterations of signaling pathways and tumour suppressor genes (TSGs) contributing to carcinogenesis. This study was aimed to examine the effect of the phytochemical, genistein on various molecular targets in HeLa cells.

METHODS: Quantitative PCR was used to analyze the expression of various molecular targets. Biochemical assays were employed to study the epigenetic enzymes. To correlate the transcriptional status of the selected TSGs and epigenetic modulation, their promoter 5'CpG methylation levels were evaluated by quantitative methylation array followed by methylation specific restriction digestion.

RESULTS: The expression of several genes involved in the cell cycle regulation, migration, inflammation, phosphatidylinositol 3-kinase (PI3K) and mitogen activated kinase-like protein (MAPK) pathway were found to be modulated includingand. Genistein modulated the expression of DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone methyltransferases (HMTs), demethylases, and histone phosphorylases. Furthermore, genistein decreased the activity of DNMTs, HDACs, and HMTs and reduced global DNA methylation levels. Promoter methylation of several TSGs, including, and, was lowered with corresponding transcriptional increase. Network analysis indicated similar effect of genistein.

CONCLUSION: This study presents a comprehensive mechanism of action of genistein showcasing effective epigenetic modulation and widespread transcriptional changes resulting in restoration of tumour suppressor gene expression. This study corroborates the development of genistein as a candidate for anti-cancer therapy.

Study Type : In Vitro Study

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