| Peroxisome proliferator-activated receptorγ ligands exert antineoplastic effects in hepatocellular carcinoma cells |
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Myung Jong Chae, Jaejun Shim, Byung-Ho Kim, Young Hwangbo, Young Ju Lee, Seung Hyung Ha, Jae Young Jang, Seok Ho Dong, Hyo Jong Kim, Young Woon Chang, Rin Chang |
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을지의과대학교 내과학교실1, 흉부외과학교실2, 영상의학교실3, 병리학교실5 |
| 원저 : Peroxisome proliferator-activated receptorγ 배위자의 간암 세포에 대한 항암 효과 |
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채명종&#;심재준&#;김병호&#;황보영&#;이영주&#;하승형&#;장재영&#;동석호&#;김효, Jaejun Shim, Byung-Ho Kim, Young Hwangbo, Young Ju Lee, Seung Hyung Ha, Jae Young Jang, Seok Ho Dong, Hyo Jong Kim, Young Woon Chang, Rin Chang |
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| Abstract |
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Background/Aims: Thiazolidinediones, which are synthetic insulin sensitizers, are known activators of peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ ligands, including endogenous 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), are thought to elicit antineoplastic effects in various cancer cells. In this study, the antineoplastic effects of PPARγ ligands against hepatocellular carcinoma (HCC) cells were investigated.
Methods: HepG2, Hep3B, and PLC/PRF5 cells were cultured with troglitazone (TGZ), pioglitazone (PGZ), rosiglitazone (RGZ), or 15d-PGJ2 at concentrations of 20-100 μM.. Cell viability, cell cycle arrest, apoptosis, and caspase activity were measured using the MTT assay, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and colorimetric assays, respectively. The effects of various caspase inhibitors were also measured using a cell death detection ELISA.
Results: All three cell lines expressed the PPARγ gene. TGZ and 15d-PGJ2 strongly inhibited growth in HepG2, Hep3B, and PLC/PRF5 cells. In contrast, PGZ and RGZ showed a much weaker effect in all cell lines. In terms of cell cycle arrest and apoptosis, TGZ induced G0/G1 arrest in HepG2 cells and increased the apoptotic fraction in Hep3B and PLC/PRF5 cells. In contrast, 15d-PGJ2 induced apoptosis only in HepG2 and Hep3B cells. TGZ and 15d-PGJ2 increased caspase-3 activity significantly and increased caspase-9 activity slightly. TGZ- and 15d-PGJ2-induced apoptoses were inhibited by a pancaspase inhibitor (Z-VAD-FMK) and a caspase-3 specific inhibitor (Z-DEVD-FMK) in a dose- dependent manner.
Conclusions: TGZ and 15d-PGJ2 elicit antineoplastic effects in various HCC cells via caspase-dependent apoptotic induction. Their differential effects on similar cell types suggest that another antineoplastic mechanism, most likely a PPARγ-independent pathway, is involved. (Korean J Med 75:288-299, 2008) |
| Key Words:
Antineoplastic agents; Hepatocellular carcinoma; Peroxisome proliferator-activated receptor gamma. |
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