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

Melina Mitsiogianni, Theodora Mantso, Dimitrios T. Trafalis, H. P. Vasantha Rupasinghe, Vasilis Zoumpourlis, Rodrigo Franco-Cruz, Sotiris Botaitis, Aglaia Pappa, Mihalis I. Panayiotidis

Research output: Contribution to journalArticle

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 (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.

Original languageEnglish (US)
JournalEuropean Journal of Nutrition
DOIs
StatePublished - Jan 1 2019

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Acetylation
Histone Deacetylases
Methylation
Lysine
Melanoma
Theoretical Models
Histone Acetyltransferases
Epigenomics
Cell Survival
Isothiocyanates
Acetyltransferases
Gene Expression Profiling
Transferases
Keratinocytes
Histones
Squamous Cell Carcinoma
Lymph Nodes
Western Blotting
allyl isothiocyanate
Gene Expression

Keywords

  • Acetyl transferases
  • Allyl isothiocyanate
  • Deacetylases
  • Histone acetylation
  • Histone methylation
  • Methyl transferases
  • Skin cancer

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma. / Mitsiogianni, Melina; Mantso, Theodora; Trafalis, Dimitrios T.; Vasantha Rupasinghe, H. P.; Zoumpourlis, Vasilis; Franco-Cruz, Rodrigo; Botaitis, Sotiris; Pappa, Aglaia; Panayiotidis, Mihalis I.

In: European Journal of Nutrition, 01.01.2019.

Research output: Contribution to journalArticle

Mitsiogianni, Melina ; Mantso, Theodora ; Trafalis, Dimitrios T. ; Vasantha Rupasinghe, H. P. ; Zoumpourlis, Vasilis ; Franco-Cruz, Rodrigo ; Botaitis, Sotiris ; Pappa, Aglaia ; Panayiotidis, Mihalis I. / Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma. In: European Journal of Nutrition. 2019.
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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 (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.",
keywords = "Acetyl transferases, Allyl isothiocyanate, Deacetylases, Histone acetylation, Histone methylation, Methyl transferases, Skin cancer",
author = "Melina Mitsiogianni and Theodora Mantso and Trafalis, {Dimitrios T.} and {Vasantha Rupasinghe}, {H. P.} and Vasilis Zoumpourlis and Rodrigo Franco-Cruz and Sotiris Botaitis and Aglaia Pappa and Panayiotidis, {Mihalis I.}",
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T1 - Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma

AU - Mitsiogianni, Melina

AU - Mantso, Theodora

AU - Trafalis, Dimitrios T.

AU - Vasantha Rupasinghe, H. P.

AU - Zoumpourlis, Vasilis

AU - Franco-Cruz, Rodrigo

AU - Botaitis, Sotiris

AU - Pappa, Aglaia

AU - Panayiotidis, Mihalis I.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Acetyl transferases

KW - Allyl isothiocyanate

KW - Deacetylases

KW - Histone acetylation

KW - Histone methylation

KW - Methyl transferases

KW - Skin cancer

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U2 - 10.1007/s00394-019-01925-6

DO - 10.1007/s00394-019-01925-6

M3 - Article

JO - European Journal of Nutrition

JF - European Journal of Nutrition

SN - 1436-6207

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