Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma

Mitsiogianni, Melina, Mantso, Theodora, Trafalis, Dimitrios, Rupasinghe, Vasantha, Zoumpourlis, Vasilis, Franco, Rodrigo, Botaitis, Sotiris, Pappa, Aglaia and Panagiotidis, Mihalis (2020) Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma. European Journal of Nutrition, 59 (2). pp. 557-569. ISSN 1436-6207

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Abstract

Objective(s): Isothiocyanates (ITCs) are biologically active plant secondary metabolites capable of mediating various biological effects including modulation of the epigenome. Our aim was to characterize the effect of allyl isothiocyanate (AITC) on lysine acetylation and methylation marks as a potential epigenetic-induced anti-melanoma strategy.

Methods: Our malignant melanoma model consisted of i) human (A375) and murine (B16-F10) malignant melanoma as well as of human ii) brain (VMM1) and lymph node (Hs 294T) metastatic melanoma, iii) non-melanoma epidermoid carcinoma (A431) and iv) immortalized keratinocyte (HaCaT) cells subjected to AITC. Cell viability, histone deacetylases (HDACs) and acetyltransferases (HATs) activities were evaluated by the Alamar blue, Epigenase HDAC Activity/Inhibition and EpiQuik HAT Activity/Inhibition assay kits respectively while their expression levels together with those of lysine acetylation and methylation marks by western immunoblotting. Finally, apoptotic gene expression was assessed by an RT-PCR-based gene expression profiling methodology.

Results: AITC reduces cell viability, decreases HDACs and HATs activities and causes changes in protein expression levels of various HDACs, HATs, and histone methyl transferases (HMTs) all of which have a profound effect on specific lysine acetylation and methylation marks. Moreover, AITC causes the induction of apoptotic cell death associated with genes involved in various apoptotic cascades.

Conclusions: AITC exerts a potent epigenetic effect suggesting its potential involvement as a promising epigenetic-induced bioactive for the treatment of malignant melanoma.

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