title: Class II-specific histone deacetylase inhibitors MC1568 and MC1575 suppress IL-8 expression in human melanoma cells.
abstract: Here, we explored the effects of the novel class II-specific histone deacetylase inhibitors (HDACis) MC1568 and MC1575 on interleukin-8 (IL-8) expression and cell proliferation in cutaneous melanoma cell line GR-M and uveal melanoma cell line OCM-3 upon stimulation with phorbol 12-myristate 13-acetate (PMA). We found that PMA upregulated IL-8 transcription via the AP-1 binding site and identified c-Jun as the transcription factor involved in this eventS. MC1568 and MC1575 inhibited IL-8 levels and cell proliferation in either unstimulated or PMA-stimulated melanoma cells. They acted by suppressing (i) c-Jun binding to the IL-8 promoter, (ii) recruitment of histones 3 and 4, RNA polymerase II and TFIIB to the c-Jun promoter, and (iii) c-Jun expression. Our findings provide new insights into mechanisms underlying anti-tumoral activities of class II-specific HDACis in human melanoma and suggest that they may constitute a novel therapeutic strategy for improving the treatment of this cancer.
authors.affiliation: Department of Experimental Specialized Medical and Surgical and Odontostomatology Sciences, University of Messina, Messina, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Venza
authors.forename: M
authors.initials: M
authors.lastname: Visalli
authors.forename: R
authors.initials: R
authors.lastname: Oteri
authors.forename: M
authors.initials: M
authors.lastname: Cucinotta
authors.forename: D
authors.initials: D
authors.lastname: Teti
authors.forename: M
authors.initials: M
authors.lastname: Venza
mesh_terms: D000107:Acetylation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D035581:Transcription Factor TFIIB / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014604:Uveal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D016209:Interleukin-8; C577554:MC1568; C583610:MC1575; D016755:Proto-Oncogene Proteins c-jun; D011758:Pyrroles; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D035581:Transcription Factor TFIIB; D012321:DNA-Directed RNA Polymerases; D006655:Histone Deacetylases; D013755:Tetradecanoylphorbol Acetate