Novel anticancer compounds induce apoptosis in melanoma cells.
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.
Bhat
Uppoor G
UG
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Zipfel
Patricia A
PA
Tyler
Douglas S
DS
Gartel
Andrei L
AL
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D045744:Cell Line, Tumor; D004357:Drug Synergism; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D009705:Nucleosides / Q000494:pharmacology* / Q000627:therapeutic use; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D013883:Thiostrepton / Q000494:pharmacology* / Q000627:therapeutic use
C509961:4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo(2,3-d)-pyrimidine-5-carboxamide; D000970:Antineoplastic Agents; D009705:Nucleosides; D010455:Peptides; D011743:Pyrimidines; C024711:siomycin A; D013883:Thiostrepton