4.6 Article

Novel anticancer compounds induce apoptosis in melanoma cells

Journal

CELL CYCLE
Volume 7, Issue 12, Pages 1851-1855

Publisher

LANDES BIOSCIENCE
DOI: 10.4161/cc.7.12.6032

Keywords

ARC; thiazole antibiotics; melanoma; Mcl-1; apoptosis; FoxM1

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We previously described the identification of a nucleoside analog transcriptional inhibitor ARC (4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-Pyrrolo[2,3-d]-pyrimidine-5-carboxamide) and FoxM1 inhibitor, thiazole antibiotic Siomycin A that were able to induce apoptosis in cancer cell lines of different origin. Here, we report the characterization of these drugs on a panel of melanoma cell lines. We found that in contrast to the common anti-melanoma drug dacarbazine (DTIC), ARC and thiazole antibiotics, Siomycin A and thiostrepton, efficiently inhibited growth and induced cell death in melanoma cell lines in low concentrations. Overexpression of the antiapoptotic protein Mcl-1 protected melanoma cells from apoptosis induced by these compounds. Furthermore, we found that ARC and Siomycin A synergistically induce apoptosis in DM833 melanoma cell line suggesting that they may antagonize different anti-apoptotic pathways in melanoma cells. In general, these drugs may represent important candidates for anti-cancer drug development against melanoma.

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