Published online Aug 15, 2003. doi: 10.3748/wjg.v9.i8.1683
Revised: December 23, 2002
Accepted: January 28, 2003
Published online: August 15, 2003
AIM: 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 µM, 15d-PGJ2 or troglitazone increased the proportion of cells with G0/G1 phase DNA content and decreased those with S phase DNA content. There was no significant change in the proportion of cells with G2/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.
CONCLUSION: The present results suggest the potential usefulness of PPAR gamma ligands for chemoprevention and treatment of liver cancers.