Differential sensitivity of human colon cancer cell lines to the nucleoside analogs ARC and DRB
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 12, 2007
- Source ID
- 10.1002/ijc.23239
Entities
People
- Andrei L. Gartel
- Uppoor G. Bhat
Organizations
- United States Department of Defense