Τίτλος:
Sulforaphane and iberin are potent epigenetic modulators of histone acetylation and methylation in malignant melanoma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objective(s): Growing evidence supports that isothiocyanates exert a wide range of bioactivities amongst of which is their capacity to interact with the epigenetic machinery in various cancers including melanoma. Our aim was to characterise the effect of sulforaphane and iberin on histone acetylation and methylation as a potential anti-melanoma strategy. Methods: We have utilised an in vitro model of malignant melanoma [consisting of human (A375, Hs294T, VMM1) and murine (B16F-10) melanoma cell lines as well as a non-melanoma (A431) and a non-tumorigenic immortalised keratinocyte (HaCaT) cell line] exposed to sulforaphane or iberin. Cell viability was evaluated by the Alamar blue assay whilst total histone deacetylases and acetyltransferases activities were determined by the Epigenase HDAC Activity/Inhibition and EpiQuik HAT Activity/Inhibition assay kits, respectively. The expression levels of specific histone deacetylases and acetyltransferases together with those of lysine acetylation and methylation marks were obtained by western immunoblotting. Results: Overall, both sulforaphane and iberin were able to (1) reduce cell viability, (2) decrease total histone deacetylase activity and (3) modulate the expression levels of various histone deacetylases as well as acetyl and methyl transferases thus modulating the acetylation and methylation status of specific lysine residues on histones 3 and 4 in malignant melanoma cells. Conclusions: Our findings highlight novel insights as to how sulforaphane and iberin differentially regulate the epigenetic response in ways compatible with their anticancer action in malignant melanoma. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.
Συγγραφείς:
Mitsiogianni, M.
Trafalis, D.T.
Franco, R.
Zoumpourlis, V.
Pappa, A.
Panayiotidis, M.I.
Περιοδικό:
European Journal of Nutrition
Εκδότης:
Springer Science and Business Media Deutschland GmbH
Λέξεις-κλειδιά:
acetic acid derivative; acyltransferase; acyltransferase inhibitor; histone deacetylase; histone H3; histone H4; iberin; lysine; methyltransferase; sulforaphane; unclassified drug; histone; histone acetyltransferase; iberin; isothiocyanic acid; sulforaphane; sulfoxide, A-375 cell line; A-431 cell line; animal cell; animal experiment; antineoplastic activity; Article; B16-F10 cell line; cell lysate; cell viability; clinical evaluation; controlled study; drug effect; drug potency; epigenetics; gene expression profiling; HaCat cell line; histone acetylation; histone methylation; Hs 294T cell line; human; human cell; in vitro study; melanoma; methylation; nonhuman; protein determination; protein expression; protein expression level; resazurin assay; Western blotting; acetylation; animal; genetic epigenesis; genetics; melanoma; metabolism; mouse, Acetylation; Animals; Epigenesis, Genetic; Histone Acetyltransferases; Histones; Humans; Isothiocyanates; Melanoma; Methylation; Mice; Sulfoxides
DOI:
10.1007/s00394-020-02227-y
