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A ligand for peroxisome proliferator activated receptor γ inhibits cell growth and induces apoptosis in human liver cancer cells
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  1. M Toyoda,
  2. H Takagi,
  3. N Horiguchi,
  4. S Kakizaki,
  5. K Sato,
  6. H Takayama,
  7. M Mori
  1. First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Gunma, Japan
  1. Correspondence to:
    Dr H Takagi, First Department of Internal Medicine, Gunma University School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371-8511, Japan;
    htakagi{at}med.gunma-u.ac.jp

Abstract

Background and aims: Induction of apoptosis of cancer cells through ligands of nuclear hormone receptors (NHRs) is a new approach in cancer therapy. Recently, one of the NHRs, peroxisome proliferator activated receptor γ (PPARγ), has been shown to influence cell growth in certain cancer cells although its effect on hepatocellular carcinoma (HCC) has not been analysed.

Methods: Experiments were conducted using three human liver cancer cell lines, PLC/PRF/5, Hep G2 and HuH-7, in vitro. These cells were exposed to troglitazone, a synthetic ligand for PPARγ, and the effects on cell growth were analysed.

Results: Expression of PPARγ mRNA was detected in all three liver cancer cell lines. Activation of PPARγ by troglitazone caused a marked growth inhibition in a dose dependent manner in three hepatoma cell lines. The DNA fragmentation ELISA assay and Hoechst 33258 staining revealed that the growth inhibitory effect by adding troglitazone was due to apoptosis of PLC/PRF/5, which strongly expressed PPARγ. Troglitazone also induced activation of the cell death protease, caspase 3, but not caspase 8, in PLC/PRF/5 cells. However, expression levels of antiapoptotic factor bcl-2 and apoptosis inducing factor bax were not affected.

Conclusion: Our study showed that PPARγ was expressed in human liver cancer cells and that the ligand for PPARγ, troglitazone, inhibited the growth of these cells by inducing apoptosis through caspase 3 activation, indicating that troglitazone could be potentially useful as an apoptosis inducer for the treatment of HCC.

  • peroxisome proliferator activated receptor γ
  • troglitazone
  • hepatocellular carcinoma
  • apoptosis
  • nuclear hormone receptors
  • NHR, nuclear hormone receptor
  • PPARγ, peroxisome proliferator activated receptor γ
  • HCC, hepatocellular carcinoma
  • NFκB, nuclear factor kappa B
  • Ab, antibody
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