RT info:eu-repo/semantics/article
T1 Involvement of PPARy in the antitumoral action of cannabinoids on hepatocellular carcinoma
A1 Rodríguez Henche, Nieves
A1 Díaz-Laviada Marturet, Inés
A1 Vara Ciruelos, Diana
A1 Morell, María Cecilia
K1 Cancer Metabolism
K1 Metabolismo del cáncer
K1 Bioquímica
K1 Biochemistry
K1 Science
K1 Ciencia
AB Cannabinoids exert antiproliferative effects in a wide range of tumoral cells, including hepatocellular carcinoma (HCC) cells. Inthis study, we examined whether the PPARc-activated pathway contributed to the antitumor effect of two cannabinoids,D9-tetrahydrocannabinol (THC) and JWH-015, against HepG2 and HUH-7 HCC cells. Both cannabinoids increased the activityand intracellular level of PPARc mRNA and protein, which was abolished by the PPARc inhibitor GW9662. Moreover, geneticablation with small interfering RNA (siRNA), as well as pharmacological inhibition of PPARc decreased the cannabinoid-inducedcell death and apoptosis. Likewise, GW9662 totally blocked the antitumoral action of cannabinoids in xenograft-induced HCCtumors in mice. In addition, PPARc knockdown with siRNA caused accumulation of the autophagy markers LC3-II and p62,suggesting that PPARc is necessary for the autophagy flux promoted by cannabinoids. Interestingly, downregulation of theendoplasmic reticulum stress-related protein tribbles homolog 3 (TRIB3) markedly reduced PPARc expression and induced p62accumulation, which was counteracted by overexpression of PPARc in TRIB3-knocked down cells. Taken together, wedemonstrate for the first time that the antiproliferative action of the cannabinoids THC and JWH-015 on HCC, in vitro and in vivo,are modulated by upregulation of PPARc-dependent pathways.
PB Nature Publishing Group
SN 2041-4889
YR 2013
FD 2013
LK http://hdl.handle.net/10017/17301
UL http://hdl.handle.net/10017/17301
LA eng
NO Ministerio de Economía y Competitividad
DS MINDS@UW
RD 24-abr-2024