Retinoic acid and its binding protein modulate apoptotic signals in hypoxic hepatocellular carcinoma cells.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Lee, J-H; Yoon, J-H; Yu, SJ; Chung, GE; Jung, EU; Kim, HY; Kim, BH; Choi, DH; Myung, SJ; Kim, YJ; Kim, CY; Lee, H-S

Published Date

  • September 28, 2010

Published In

Volume / Issue

  • 295 / 2

Start / End Page

  • 229 - 235

PubMed ID

  • 20350780

Electronic International Standard Serial Number (EISSN)

  • 1872-7980

Digital Object Identifier (DOI)

  • 10.1016/j.canlet.2010.03.005


  • eng

Conference Location

  • Ireland