ARC synergizes with ABT-737 to induce apoptosis in human cancer cells.
Previously, we reported that the nucleoside analogue/transcriptional inhibitor ARC (4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo(2,3-d)-pyrimidine-5-carboxamide) was able to induce p53-independent apoptosis in multiple cancer cell lines of different origins. This occurred, at least in part, by the suppression of short-lived, prosurvival member of the Bcl-2 family, Mcl-1. In contrast, we show here that treatment of human cancer cells with the pan-Bcl-2 inhibitor ABT-737 alone led to upregulation of Mcl-1 protein expression. Combination of subapoptotic concentrations of ABT-737 and ARC induced mitochondrial injury and potent caspase-3/caspase-9-dependent apoptosis in a wide variety of human cancer cell lines. These data suggest that the ABT-737/ARC combination, which simultaneously targets Bcl-2 and Mcl-1, may be efficient against human cancer.
Bhat
Uppoor G
UG
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Pandit
Bulbul
B
Gartel
Andrei L
AL
D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D009596:Nitrophenols / Q000494:pharmacology*; D009705:Nucleosides / Q000494:pharmacology*; D010799:Phycoerythrin / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D013194:Staining and Labeling; D013449:Sulfonamides / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
C509961:4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo(2,3-d)-pyrimidine-5-carboxamide; C501332:ABT-737; D017304:Annexin A5; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D009596:Nitrophenols; D009705:Nucleosides; D010879:Piperazines; D011743:Pyrimidines; D013449:Sulfonamides; D010799:Phycoerythrin; D020169:Caspases