Sulforaphane and iberin are potent epigenetic modulators of histone acetylation and methylation in malignant melanoma.

Eur J Nutr

Faculty of Health and Life Sciences, Department of Applied Sciences, Group of Translational Biosciences, Northumbria University, Newcastle Upon Tyne, NE1 8ST, UK.

Published: February 2021

AI Article Synopsis

  • Isothiocyanates like sulforaphane and iberin can affect epigenetic mechanisms in melanoma, potentially serving as an anti-cancer strategy.
  • Researchers used various melanoma and non-melanoma cell lines to study the impacts of these compounds on cell viability and histone modification processes.
  • Results showed that both compounds reduced cell viability, decreased histone deacetylase activity, and altered the expression of histone-modifying enzymes, which suggests a specific epigenetic regulation in cancer cells.

Article Abstract

Objective(s): Growing evidence supports that isothiocyanates exert a wide range of bioactivities amongst of which is their capacity to interact with the epigenetic machinery in various cancers including melanoma. Our aim was to characterise the effect of sulforaphane and iberin on histone acetylation and methylation as a potential anti-melanoma strategy.

Methods: We have utilised an in vitro model of malignant melanoma [consisting of human (A375, Hs294T, VMM1) and murine (B16F-10) melanoma cell lines as well as a non-melanoma (A431) and a non-tumorigenic immortalised keratinocyte (HaCaT) cell line] exposed to sulforaphane or iberin. Cell viability was evaluated by the Alamar blue assay whilst total histone deacetylases and acetyltransferases activities were determined by the Epigenase HDAC Activity/Inhibition and EpiQuik HAT Activity/Inhibition assay kits, respectively. The expression levels of specific histone deacetylases and acetyltransferases together with those of lysine acetylation and methylation marks were obtained by western immunoblotting.

Results: Overall, both sulforaphane and iberin were able to (1) reduce cell viability, (2) decrease total histone deacetylase activity and (3) modulate the expression levels of various histone deacetylases as well as acetyl and methyl transferases thus modulating the acetylation and methylation status of specific lysine residues on histones 3 and 4 in malignant melanoma cells.

Conclusions: Our findings highlight novel insights as to how sulforaphane and iberin differentially regulate the epigenetic response in ways compatible with their anticancer action in malignant melanoma.

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Source
http://dx.doi.org/10.1007/s00394-020-02227-yDOI Listing

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