Novel anticancer compounds induce apoptosis in melanoma cells.

Abstract

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, Patricia A Zipfel, Douglas S Tyler, Andrei L Gartel
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 7 Issue 12 Pg. 1851-5 (Jun 15 2008) ISSN: 1551-4005 [Electronic] United States
• PMID: 18583930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo(2,3-d)-pyrimidine-5-carboxamide
• Antineoplastic Agents
• Nucleosides
• Peptides
• Pyrimidines
• siomycin A
• Thiostrepton

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis
• Cell Line, Tumor
• Drug Synergism
• Humans
• Melanoma (drug therapy, pathology)
• Nucleosides (pharmacology, therapeutic use)
• Peptides (pharmacology, therapeutic use)
• Pyrimidines (pharmacology, therapeutic use)
• Thiostrepton (pharmacology, therapeutic use)