Antineoplastic action of sulforaphane on HeLa cells by modulation of signaling pathways and epigenetic pathways.

Minerva medica
Madhumitha K SundaramShafiul Haque

Abstract

Epigenetic modifications alter signaling and molecular pathways and are an important therapeutic target. This study examined the effect of sulforaphane on molecular targets in HeLa cells. Quantitative PCR of various molecular targets was performed. Activity of epigenetic enzymes was measured by ELISA and molecular docking analysis was conducted. Promoter methylation of some tumour suppressor genes was quantified using PCR based methylation array. In-silico protein-protein interaction network analysis was performed to understand the effect of transcriptional changes. Quantitative PCR demonstrated the transcriptional modulation of genes involved in proliferation, metastasis, inflammation, signal transduction pathways and chromatin modifiers. Sulforaphane reduced the enzymatic activity of DNA methyl transferases, histone deacetylases and histone methyltransferases. Molecular docking results suggest that sulforaphane competitively inhibited several DNA methyl transferases and histone deacetylases. Promoter 5'CpG methylation levels of selected tumour suppressor genes was found to be reduced which correlated with their transcriptional increase as well modulation of epigenetic enzymes. Further, protein-protein interaction network anal...Continue Reading

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