Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma
Autor: | Melina Mitsiogianni, Mihalis I. Panayiotidis, Vasilis Zoumpourlis, Rodrigo Franco, Theodora Mantso, Aglaia Pappa, Dimitrios T. Trafalis, H.P. Vasantha Rupasinghe, Sotiris Botaitis |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Blotting Western Medicine (miscellaneous) 030209 endocrinology & metabolism Methylation Histone methylation Mice 03 medical and health sciences 0302 clinical medicine Isothiocyanates Allyl isothiocyanate Skin cancer Animals Humans Epigenetics Viability assay Melanoma Cells Cultured 030109 nutrition & dietetics Nutrition and Dietetics biology Chemistry Deacetylases Lysine Acetylation Original Contribution Acetyl transferases C900 Disease Models Animal HaCaT Methyl transferases Histone Histone acetylation Epidermoid carcinoma biology.protein Cancer research |
Zdroj: | European Journal of Nutrition |
ISSN: | 1436-6207 |
Popis: | 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 (1) human (A375) and murine (B16-F10) malignant melanoma as well as of human; (2) brain (VMM1) and lymph node (Hs 294T) metastatic melanoma; (3) non-melanoma epidermoid carcinoma (A431) and (4) 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 regulates the expression of a number of genes participating in various apoptotic cascades thus indicating its involvement in apoptotic induction. Conclusions AITC exerts a potent epigenetic effect suggesting its potential involvement as a promising epigenetic-induced bioactive for the treatment of malignant melanoma. |
Databáze: | OpenAIRE |
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