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.
Retinoic acid and its binding protein modulate apoptotic signals in hypoxic hepatocellular carcinoma cells
Riferimento:
Cancer Lett. 2010Sep 28;295(2):229-35.
Autori:
Lee JH, Yoon JH, Yu SJ, Chung GE, Jung EU, Kim HY, Kim BH, Choi DH, Myung SJ, Kim YJ, Kim CY, Lee HS.
Fonte:
Cancer Lett. 2010Sep 28;295(2):229-35.
Anno:
2010
Azione:
L'acido retinoico (RA) e la modulazione del segnale dell'acido retinoico cellulare ligando proteina-II (CRABP-II) sono terapeuticamente implicati nel carcinoma epatocellulare (HCC) infiltrativo esposto a ipossia.
Target:
RA/CRABP-II/carcinoma epatocellulare.
Sostanze: