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

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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Acknowledgements

This work was supported by (1) start-up funds (MIP) including a Ph.D. studentship (MM) provided by the Multi-Disciplinary Research Theme in “Bio-economy” of Northumbria University; (2) an LLP Erasmus Program (AP) and (3) an “OPENSCREEN-GR: An Open-Access Research Infrastructure of Target-Based Screening Technologies and Chemical Biology for Human & Animal Health, Agriculture & Environment (MIS 5002691)” implemented under the action “Reinforcement of the Research and Innovation Infrastructure” funded by the Operational Program “Competitiveness, Entrepreneurship and Innovation (NSRF 2014–2020)” co-financed by Greece and the European Union (under the European Regional Development Fund) (AP).

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Correspondence to Mihalis I. Panayiotidis.

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Mitsiogianni, M., Trafalis, D.T., Franco, R. et al. Sulforaphane and iberin are potent epigenetic modulators of histone acetylation and methylation in malignant melanoma. Eur J Nutr 60, 147–158 (2021). https://doi.org/10.1007/s00394-020-02227-y

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Keywords

  • Isothiocyanates
  • Sulforaphane
  • Iberin
  • Melanoma
  • Epigenetics
  • Acetyl transferases
  • Deacetylases
  • Methyl transferases
  • Lysine methylation
  • Lysine acetylation