• Minerva medica · Dec 2021

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

    • Madhumitha Kedhari Sundaram, Abdulmajeed G Almutary, Ahmad Alsulimani, Syed Rehan Ahmad, Pallavi Somvanshi, Tulika Bhardwaj, Rinaldo Pellicano, Sharmila Fagoonee, Arif Hussain, and Shafiul Haque.
    • School of Life Sciences, Manipal Academy of Higher Education, Dubai, United Arab Emirates.
    • Minerva Med. 2021 Dec 1; 112 (6): 792-803.

    BackgroundEpigenetic modifications alter signaling and molecular pathways; moreover, they are an important therapeutic target. This study examined the effect of sulforaphane on molecular targets in HeLa cells.MethodsQuantitative 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 tumor 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.ResultsQuantitative 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 tumor suppressor genes was found to be reduced which correlated with their transcriptional increase as well modulation of epigenetic enzymes. Further, protein-protein interaction network analysis discerned the participation of genes towards cancer pathways. Functional enrichment and pathway-based analysis represented the modulation of epigenetic and signaling pathways on sulforaphane treatment.ConclusionsThe modulation in transcriptional status of epigenetic regulators, genes involved in tumorigenesis resulting in tumor suppressor genes demethylation and re-expression underscores the mechanism behind the anticancer effect of sulforaphane on HeLa cells.

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