TY - JOUR
TI - Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma
AU - Mitsiogianni, M.
AU - Mantso, T.
AU - Trafalis, D.T.
AU - Vasantha Rupasinghe, H.P.
AU - Zoumpourlis, V.
AU - Franco, R.
AU - Botaitis, S.
AU - Pappa, A.
AU - Panayiotidis, M.I.
JO - European Journal of Nutrition
PY - 2020
VL - 59
TODO - 2
SP - 557-569
PB - Springer-Verlag
SN - 1436-6207, 1436-6215
TODO - 10.1007/s00394-019-01925-6
TODO - acyltransferase;  allyl isothiocyanate;  anacardic acid;  caspase 9;  decitabine;  f2rl3 protein;  Fas ligand;  histone acetyltransferase PCAF;  histone deacetylase;  histone deacetylase 4;  histone deacetylase 6;  histone methyltransferase;  interleukin 2;  interleukin 6;  lysine;  panobinostat;  protein kinase C beta;  protein MDM2;  unclassified drug;  allyl isothiocyanate;  isothiocyanic acid derivative;  lysine, A-375 cell line;  animal cell;  antineoplastic activity;  apoptosis;  Article;  cell viability;  clinical assessment;  clinical evaluation;  controlled study;  drug effect;  enzyme activity;  epigenetics;  gene expression;  gene expression profiling;  HaCat cell line;  histone acetylation;  histone methylation;  human;  human cell;  immunoblotting;  lymph node metastasis;  melanoma;  metastatic melanoma;  nonhuman;  protein expression level;  real time polymerase chain reaction;  resazurin assay;  squamous cell carcinoma;  acetylation;  animal;  cell culture;  disease model;  drug effect;  melanoma;  metabolism;  methylation;  mouse;  Western blotting, Acetylation;  Animals;  Blotting, Western;  Cells, Cultured;  Disease Models, Animal;  Humans;  Isothiocyanates;  Lysine;  Melanoma;  Methylation;  Mice
TODO - 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. © 2019, The Author(s).
ER -