Peroxisome proliferator-activated receptor gamma ligands inhibit cell growth and induce apoptosis in human liver cancer BEL-7402 cells.
OBJECTIVE
To investigate the characteristics of PPAR gamma ligands induced apoptosis in liver cancer cells.


METHODS
The effects of ligands for each of the PPAR gamma ligands on DNA synthesis and cell viability were examined in BEL-7402 liver cancer cells. Apoptosis was characterized by Hochest33258 staining, DNA fragmentation, TUNEL and ELISA, and cell cycle kinetics by FACS. Modulation of apoptosis related caspases expression by PPAR gamma ligands was examined by Western blot.


RESULTS
PPARgamma ligands, 15-deoxy-(12), (14)-prostaglandin J2 (15d-PGJ2) and troglitazone (TGZ), suppressed DNA synthesis of BEL-7402 cells. Both 15d-PGJ2 and TGZ induced BEL-7402 cell death in a dose dependent manner, which was associated with an increase in fragmented DNA and TUNEL-positive cells. At concentrations of 10 and 30 microM, 15d-PGJ(2) or troglitazone increased the proportion of cells with G(0)/G(1) phase DNA content and decreased those with S phase DNA content. There was no significant change in the proportion of cells with G(2)/M DNA content. The activities of Caspases-3, -6, -7 and -9 were increased by 15d-PGJ2 and TGZ treatment, while the activity of Caspase 8 had not significantly changed.


CONCLUSIONS
The present results suggest the potential usefulness of PPAR gamma ligands for chemoprevention and treatment of liver cancers.
Li
Ming-Yi
MY
Department of General Surgery, Affiliated Hospital of Guangdong Medical College, Zhangjiang 524001, Guangdong Province, China. zjmyli@sohu.com
Deng
Hua
H
Zhao
Jia-Ming
JM
Dai
Dong
D
Tan
Xiao-Yu
XY
D017209:Apoptosis; D002455:Cell Division; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors