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

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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Lee JH,Yoon JH,Yu SJ,Chung GE,Jung EU,Kim HY,Kim BH,Choi DH,Myung SJ,Kim YJ,Kim CY,Lee HS

doi

10.1016/j.canlet.2010.03.005

subject

Has Abstract

pub_date

2010-09-28 00:00:00

pages

229-35

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(10)00142-4

journal_volume

295

pub_type

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