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• W1974451567 startingPage "756" @default.
• W1974451567 abstract "Melanoma incidence and mortality rates continue to increase each year. Lack of clinically viable agents, drug combinations, effective targeted delivery approaches and success inhibiting targets in tumor tissue have made this disease one of the most difficult to treat, which makes prevention an important option for decreasing disease incidence and mortality rates. Inhibiting histone deacetylases (HDAC) is an approach currently being explored to more effectively treat melanoma but use for prevention has not been explored. In this study, novel selenium containing derivatives of the FDA approved HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) called 5-phenylcarbamoylpentyl selenocyanide (PCP-SeCN) and Bis{5-phenylcarbamoylpentyl} diselenide (B(PCP)-2Se) were created and efficacy tested for preventing early melanocytic lesion development in skin. Topical application of PCP-SeCN and B(PCP)-2Se inhibited melanocytic lesion development in laboratory-generated skin by up to 87% with negligible toxicological effect. Mechanistically, PCP-SeCN and B(PCP)-2Se inhibited HDAC activity and had new inhibitory properties by moderating Akt activity to induce cellular apoptosis as demonstrated by an increase in the sub-G0-G1 cell population, and cleaved caspase-3 as well as PARP levels. Furthermore, PCP-SeCN and B(PCP)-2Se inhibited cell proliferation by inhibiting cyclin D1 expression and increasing p21 levels. Thus, PCP-SeCN and B(PCP)-2Se are potential melanoma chemopreventive agents with enhanced efficacy compared with SAHA due to new PI3 kinase pathway inhibitory properties." @default.
• W1974451567 created "2016-06-24" @default.
• W1974451567 creator A5007749446 @default.
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• W1974451567 creator A5087345379 @default.
• W1974451567 date "2012-07-01" @default.
• W1974451567 modified "2023-10-11" @default.
• W1974451567 title "Selenium-containing histone deacetylase inhibitors for melanoma management" @default.
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• W1974451567 doi "https://doi.org/10.4161/cbt.20558" @default.
• W1974451567 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3399702" @default.
• W1974451567 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22669577" @default.
• W1974451567 hasPublicationYear "2012" @default.
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