Journal
CANCER LETTERS
Volume 295, Issue 2, Pages 229-235Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2010.03.005
Keywords
Cellular retinoic acid binding protein-II; Retinoic acid; Hepatocellular carcinoma; Apoptosis; Hypoxia
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Funding
- Korea Health 21 RD Project [0412-CR01-0704-0001]
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Hypoxia induces survival signals in hepatocellular carcinoma (HCC). We attempted to find a hypoxia-induced signal that could be used for modulating HCC cell death. Cellular retinoic acid binding protein-II (CRABP-II) expression was significantly increased in hypoxic HCC cells. Treatment with retinoic acid (RA), a ligand for CRABP-II, induced HCC cell apoptosis more effectively in hypoxia than in normoxia, whereas hypoxia-induced CRABP-II expression attenuated RA-induced apoptosis. Inhibition of CRABP-II enhanced RA-induced apoptosis and sensitized RA-resistant HCC cells to RA cytotoxicity by attenuating p42/44 MAPK and Akt activation. Therefore, RA/CRABP-II signal modulation is therapeutically implicated in infiltrative HCCs exposed to hypoxia. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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