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Differential sensitivity of human colon cancer cell lines to the nucleoside analogs ARC and DRB

✍ Scribed by Uppoor G. Bhat; Andrei L. Gartel

Publisher
John Wiley and Sons
Year
2007
Tongue
French
Weight
193 KB
Volume
122
Category
Article
ISSN
0020-7136

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✦ Synopsis

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.

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