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Reports

Novel anticancer compounds induce apoptosis in melanoma cells

Uppoor G. Bhat, Patricia A. Zipfel, Douglas S. Tyler and Andrei L. Gartel

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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.

Authors

Uppoor G. Bhat

University of Illinois at Chicago; Chicago, IL

Patricia A. Zipfel

Duke University Medical Center; Durham, NC

Douglas S. Tyler

Duke University Medical Center; Durham, NC

Andrei L. Gartel

University of Illinois at Chicago; Chicago, IL

Purchase article for $19

Subscribe to this journal for $129/year