Involvement of PPARα and PPARγ in apoptosis and proliferation of human hepatocarcinoma HepG2 cells

Peroxisome proliferator-activated receptors (PPARs) mediate the effects of various ligands, known as peroxisome proliferators, a heterogeneous class of compounds including industrial chemicals, pharmaceuticals, and biomolecules such as fatty acids and eicosanoids. Among peroxisome proliferators, fibrate derivatives are considered specific ligands for PPAR alpha, whereas eicosanoids, such as PGJ2, for PPAR gamma. The study aimed to clarify the relation between PPARs and apoptosis or proliferation on the same type of cells, using clofibrate as specific ligand of PPAR alpha and PGJ2 as specific ligand of PPAR gamma. The cells used were human hepatocarcinoma HepG2 cells. The results showed that PPAR alpha protein content increased in HepG2 cells treated with clofibrate, causing apoptosis in a time- and concentration-dependent way, as evidenced by the citofluorimetric assay and determination of BAD, myc and protein phosphatase 2A protein content. It also emerged that PPAR gamma increased in the same cells when treated with a specific ligand of this PPAR; in this case the increase of PPAR gamma did not cause an increase of apoptosis, but a time- and concentration-dependent inhibition of cell proliferation, evidenced by decreased cell numbers and increased number of cells in the G0/G1 phase of the cycle. It may be concluded that PPAR alpha is chiefly related to apoptosis and PPAR gamma to cell proliferation. Copyright (C) 2010 John Wiley & Sons, Ltd.