Novel anticancer compounds induce apoptosis in melanoma cells

被引:71
作者
Bhat, Uppoor G. [1 ]
Zipfel, Patricia A. [2 ,3 ]
Tyler, Douglas S. [2 ,3 ]
Gartel, Andrei L. [1 ]
机构
[1] Univ Illinois, Dept Med, Chicago, IL 60612 USA
[2] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
[3] Durham Vet Affairs Med Ctr, Dept Surg, Durham, NC USA
关键词
ARC; thiazole antibiotics; melanoma; Mcl-1; apoptosis; FoxM1;
D O I
10.4161/cc.7.12.6032
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1851 / 1855
页数:5
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