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

Melina Mitsiogianni; Theodora Mantso; Dimitrios Trafalis; Vasantha Rupasinghe; Vasilis Zoumpourlis; Rodrigo Franco; Sotiris Botaitis; Aglaia Pappa; Mihalis Panagiotidis

doi:10.1007/s00394-019-01925-6

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

Melina Mitsiogianni, Theodora Mantso, Dimitrios Trafalis, Vasantha Rupasinghe, Vasilis Zoumpourlis, Rodrigo Franco, Sotiris Botaitis, Aglaia Pappa, Mihalis Panagiotidis

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

59 Downloads (Pure)

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.

Original language	English
Pages (from-to)	557-569
Number of pages	13
Journal	European Journal of Nutrition
Volume	59
Issue number	2
Early online date	14 Feb 2019
DOIs	https://doi.org/10.1007/s00394-019-01925-6
Publication status	Published - Mar 2020

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1007/s00394-019-01925-6Licence: CC BY

Mitsiogianni2019_Article_AllylIsothiocyanateRegulatesLyFinal published version, 1.95 MBLicence: CC BY
Mitsiogianni2020_Article_AllylIsothiocyanateRegulatesLyFinal published version, 1.93 MBLicence: CC BY

Cite this

@article{ccc351c1168741a388822f94161127d7,

title = "Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma",

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.",

keywords = "Allyl isothiocyanate, Skin cancer, Acetyl transferases, Deacetylases, Methyl transferases, Histone acetylation, Histone methylation",

author = "Melina Mitsiogianni and Theodora Mantso and Dimitrios Trafalis and Vasantha Rupasinghe and Vasilis Zoumpourlis and Rodrigo Franco and Sotiris Botaitis and Aglaia Pappa and Mihalis Panagiotidis",

year = "2020",

month = mar,

doi = "10.1007/s00394-019-01925-6",

language = "English",

volume = "59",

pages = "557--569",

journal = "European Journal of Nutrition",

issn = "1436-6207",

publisher = "Springer",

number = "2",

}

TY - JOUR

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

AU - Rupasinghe, Vasantha

AU - Zoumpourlis, Vasilis

AU - Franco, Rodrigo

AU - Botaitis, Sotiris

AU - Pappa, Aglaia

AU - Panagiotidis, Mihalis

PY - 2020/3

Y1 - 2020/3

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 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.

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 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.

KW - Allyl isothiocyanate

KW - Skin cancer

KW - Acetyl transferases

KW - Deacetylases

KW - Methyl transferases

KW - Histone acetylation

KW - Histone methylation

UR - https://www.scopus.com/pages/publications/85061649293

U2 - 10.1007/s00394-019-01925-6

DO - 10.1007/s00394-019-01925-6

M3 - Article

SN - 1436-6207

VL - 59

SP - 557

EP - 569

JO - European Journal of Nutrition

JF - European Journal of Nutrition

IS - 2

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this