当前位置： SCI文献检索 > CANCER期刊下所有文献 > Peroxisome proliferator-activated receptor gamma ligand troglitazone induces cell cycle arrest and apoptosis of hepatocellular carcinoma cell lines.

Peroxisome proliferator-activated receptor gamma ligand troglitazone induces cell cycle arrest and apoptosis of hepatocellular carcinoma cell lines.

Abstract：

BACKGROUND:Ligand activation of peroxisome proliferator-activated receptor gamma (PPARgamma) results in the inhibition of proliferation of various cancer cells. The aim of this study is to investigate the mechanisms of cell growth inhibition of hepatocellular carcinoma (HCC) cell lines by the PPARgamma ligand, troglitazone. METHODS:Six HCC cell lines were used to study the effects of troglitazone on cell growth by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, on cell cycle by flow cytometry, and on the cell cycle-regulating factors of late G1 phase by Western blotting. Apoptosis assays were performed by flow cytometry using membrane, nuclear, cytoplasmic, and mitochondrial markers. Caspase inhibitors were used to analyze the mechanisms of apoptosis induced by troglitazone. RESULTS:Troglitazone showed a potent dose-dependent effect on the growth inhibition of all six HCC cell lines, which were suppressed to under 50% of control at the concentration of 10 micromol/L. The growth inhibition was linked to the G1 phase cell cycle arrest through the up-expression of the cyclin-dependent kinase inhibitors, p21 and p27 proteins, and the hypophosphorylation of retinoblastoma protein. Troglitazone induced apoptosis by caspase-dependent (mitchondrial transmembrane potential decrease, cleavage of poly [adenosine diphosphate ribose] polymerase, 7A6 antigen exposure, Bcl-2 decrease, and activation of caspase 3) and caspase-independent (phosphatidylserine externalization) mechanisms. CONCLUSIONS:Our data suggest that ligand activation of PPARgamma by troglitazone or modified analogs of the thiazolidinedione class of drugs is a novel target for effective therapy against HCC, because of the significant antiproliferative and programmed cell death induction capabilities demonstrated by troglitazone.

journal_name

Cancer

journal_title

Cancer

authors

Yoshizawa K,Cioca DP,Kawa S,Tanaka E,Kiyosawa K

doi

10.1002/cncr.10906

subject

Has Abstract

pub_date

2002-11-15 00:00:00

pages

2243-51

issue

eissn

0008-543X

issn

1097-0142

journal_volume

pub_type

杂志文章

在线工具

Peroxisome proliferator-activated receptor gamma ligand troglitazone induces cell cycle arrest and apoptosis of hepatocellular carcinoma cell lines.