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Retinoic acid and its binding protein modulate apoptotic signals in hypoxic hepatocellular carcinoma cells
Cited 8 time in
Web of Science
Cited 11 time in Scopus
- Authors
- Issue Date
- 2010-09-28
- Publisher
- ELSEVIER IRELAND LTD
- Citation
- CANCER LETTERS; Vol.295 2; 229-235
- Keywords
- Cellular retinoic acid binding protein-II ; Hepatocellular carcinoma ; Retinoic acid ; Apoptosis ; Hypoxia
- Abstract
- 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.
- ISSN
- 0304-3835
- Language
- English
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