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Class II ‐specific histone deacetylase inhibitors MC 1568 and MC 1575 suppress IL ‐8 expression in human melanoma cells
Author(s) -
Venza I.,
Visalli M.,
Oteri R.,
Cucinotta M.,
Teti D.,
Venza M.
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12049
Subject(s) - histone deacetylase , melanoma , cancer research , microbiology and biotechnology , transcription factor , transcription (linguistics) , histone deacetylase 5 , cell growth , biology , cell culture , chemistry , histone , gene , biochemistry , genetics , linguistics , philosophy
Summary Here, we explored the effects of the novel class II ‐specific histone deacetylase inhibitors ( HDAC is) MC 1568 and MC 1575 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. MC 1568 and MC 1575 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 HDAC is in human melanoma and suggest that they may constitute a novel therapeutic strategy for improving the treatment of this cancer.