Differential sensitivity of human colon cancer cell lines to the nucleoside analogs ARC and DRB
Article first published online: 12 NOV 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 122, Issue 6, pages 1426–1429, 15 March 2008
How to Cite
Bhat, U. G. and Gartel, A. L. (2008), Differential sensitivity of human colon cancer cell lines to the nucleoside analogs ARC and DRB. Int. J. Cancer, 122: 1426–1429. doi: 10.1002/ijc.23239
- Issue published online: 21 JAN 2008
- Article first published online: 12 NOV 2007
- Manuscript Accepted: 21 SEP 2007
- Manuscript Received: 27 AUG 2007
- Department of Defense. Grant Numbers: CM064025, BC052816
Recently, we identified a nucleoside analog named ARC (4-amino-6-hydrazino-7-β-D-ribofuranosyl-7H-Pyrrolo[2,3-d]pyrimidine-5-carboxamide), which has the properties of a general transcriptional inhibitor. Here, we report the characterization of ARC on a panel of colorectal cancer (CRC) cell lines. Cell death induced by ARC in CRC cells was accompanied by caspase-3 cleavage and correlated with the downregulation of antiapoptotic proteins, survivin and Mcl-1 and with the inhibition of Akt phosphorylation. At the same time, colon cancer cell lines were resistant to the well–known nucleoside analog DRB (5,6-dichloro-1-β-D-ribofuranosylbenzimidazole), which failed to downregulate Mcl-1 or survivin. Overall, ARC could represent an attractive candidate for anti-cancer drug development that targets multiple survival pathways in colon cancer cells. © 2007 Wiley-Liss, Inc.