Affordable Access

Publisher Website

Involvement of PPARγ in the antitumoral action of cannabinoids on hepatocellular carcinoma

Authors
Journal
Cell Death and Disease
2041-4889
Publisher
Nature Publishing Group
Publication Date
Volume
4
Issue
5
Identifiers
DOI: 10.1038/cddis.2013.141
Keywords
  • Original Article
Disciplines
  • Biology
  • Pharmacology

Abstract

Cannabinoids exert antiproliferative effects in a wide range of tumoral cells, including hepatocellular carcinoma (HCC) cells. In this study, we examined whether the PPARγ-activated pathway contributed to the antitumor effect of two cannabinoids, Δ9-tetrahydrocannabinol (THC) and JWH-015, against HepG2 and HUH-7 HCC cells. Both cannabinoids increased the activity and intracellular level of PPARγ mRNA and protein, which was abolished by the PPARγ inhibitor GW9662. Moreover, genetic ablation with small interfering RNA (siRNA), as well as pharmacological inhibition of PPARγ decreased the cannabinoid-induced cell death and apoptosis. Likewise, GW9662 totally blocked the antitumoral action of cannabinoids in xenograft-induced HCC tumors in mice. In addition, PPARγ knockdown with siRNA caused accumulation of the autophagy markers LC3-II and p62, suggesting that PPARγ is necessary for the autophagy flux promoted by cannabinoids. Interestingly, downregulation of the endoplasmic reticulum stress-related protein tribbles homolog 3 (TRIB3) markedly reduced PPARγ expression and induced p62 accumulation, which was counteracted by overexpression of PPARγ in TRIB3-knocked down cells. Taken together, we demonstrate 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 PPARγ-dependent pathways.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments

More articles like this

In vitro and in vivo antitumoral action of metform...

on Hepatology research : the offi... September 2012

Anti-tumoral action of cannabinoids on hepatocellu...

on Cell Death and Differentiation July 2011

Antitumoral effect of celecoxib in hepatocellular...

on Journal of Clinical Oncology Jul 20, 2005
More articles like this..