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PPARgamma pathway activation results in apoptosis and COX-2 inhibition in HepG2 cells

Ming-Yi Li1, Hua Deng, Jia-Ming Zhao

  • 1Department of General Surgery,Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China. zjmyli@sohu.com

World Journal of Gastroenterology
|June 12, 2003
PubMed
Abstract

Insights

Troglitazone (TGZ) inhibits liver cancer cell growth and induces apoptosis in HepG2 cells. This effect involves caspase-3 activation and altered expression of key proteins like COX-2, Bcl-2, Bax, and Bak.

Area of Science:

  • Hepatocellular Carcinoma Research
  • Molecular Biology
  • Drug Discovery

Background:

  • Liver cancer, specifically hepatocellular carcinoma (HCC), remains a significant global health challenge.
  • Identifying novel therapeutic agents that can inhibit cancer cell proliferation and induce apoptosis is crucial for effective treatment strategies.

Purpose of the Study:

  • To investigate the anti-cancer effects of troglitazone (TGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, on the human liver cancer cell line HepG2.
  • To elucidate the molecular mechanisms underlying TGZ-induced apoptosis and inhibition of cell proliferation.

Main Methods:

  • Cell viability was assessed using MTT assays.
  • DNA synthesis was measured by ((3)H) thymidine incorporation.
  • Apoptosis was detected via Hochest33258 staining and DNA ladder assays.
  • Gene and protein expression levels were analyzed using RT-PCR, Northern blotting, and Western blotting.
  • Enzyme-linked immunosorbent assay (ELISA) was used to quantify prostaglandin E2 (PGE2) levels.
  • Caspase-3 activity was measured.

Main Results:

  • Troglitazone significantly inhibited HepG2 cell proliferation and induced apoptosis.
  • TGZ treatment led to the down-regulation of cyclooxygenase-2 (COX-2) mRNA and protein, and Bcl-2 protein expression.
  • Conversely, the expression of pro-apoptotic proteins Bax and Bak was up-regulated, and caspase-3 activity was elevated.
  • A transient decrease in prostaglandin E2 (PGE2) levels was observed after 12 hours of TGZ treatment.

Conclusions:

  • Troglitazone demonstrates potent anti-cancer properties against HepG2 liver cancer cells by inhibiting proliferation and inducing apoptosis.
  • The observed effects are likely mediated by the activation of caspase-3-like proteases.
  • Modulation of key molecular targets, including down-regulation of COX-2 and Bcl-2, up-regulation of Bax and Bak, and altered PGE2 levels, contributes to TGZ's anti-cancer activity.

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