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

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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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Authors and Affiliations

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

    Melina Mitsiogianni & Mihalis I. Panayiotidis

  2. Laboratory of Pharmacology, Clinical Pharmacology Unit, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece

    Dimitrios T. Trafalis

  3. Redox Biology Centre, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA

    Rodrigo Franco

  4. School of Veterinary Medicine & Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA

    Rodrigo Franco

  5. Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 11635, Athens, Greece

    Vasilis Zoumpourlis

  6. Department of Molecular Biology and Genetics, Democritus University of Thrace, 68100, Alexandroupolis, Greece

    Aglaia Pappa

  7. Department of Electron Microscopy and Molecular Pathology, The Cyprus Institute of Neurology and Genetics, 2371, Nicosia, Cyprus

    Mihalis I. Panayiotidis

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  1. Melina Mitsiogianni
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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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