title: Sirtuin deacetylases: a new target for melanoma management.
abstract: Melanoma continues to cause more deaths than any other skin cancer, necessitating the development of new avenues of treatment. One promising new opportunity comes in the form of mechanism-based therapeutic targets. We recently reported the overexpression and delocalization of the class III histone deacetylase SIRT1 in melanoma, and demonstrated that its small molecule inhibition via Tenovin-1 decreased cell growth and viability of melanoma cells, possibly by a p53 mediated induction of p21. Here, we support our data using additional SIRT inhibitors, viz. Sirtinol and Ex-527, which suggests possible benefits of concomitantly inhibiting more than one Sirtuin for an effective cancer management strategy. This "Extra View" paper also includes a discussion of our results in the context of similar recent and concurrent studies. Furthermore, we expand upon our findings in an analysis of new research that may link the cellular localization and growth effects of SIRT1 with the PI3K signaling pathway.
authors.affiliation: a Department of Dermatology ; University of Wisconsin; Madison , WI USA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Wilking
authors.forename: Chandra K
authors.initials: CK
authors.lastname: Singh
authors.forename: Minakshi
authors.initials: M
authors.lastname: Nihal
authors.forename: Mary A
authors.initials: MA
authors.lastname: Ndiaye
authors.forename: Nihal
authors.initials: N
authors.lastname: Ahmad
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use*; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D056545:Group III Histone Deacetylases / Q000037:antagonists & inhibitors*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009284:Naphthols / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D001549:Benzamides; D002227:Carbazoles; D009284:Naphthols; C439060:sirtinol; D056545:Group III Histone Deacetylases
keywords: PI3K; SIRT1; SIRT1 inhibitors; cellular localization; melanoma