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 PPARα, whereas eicosanoids, such as PGJ2, for PPARγ. 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 PPARα and PGJ2 as specific ligand of PPARγ. The cells used were human hepatocarcinoma HepG2 cells. The results showed that PPARα 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 PPARγ increased in the same cells when treated with a specific ligand of this PPAR; in this case the increase of PPARγ 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 PPARα is chiefly related to apoptosis and PPARγ to cell proliferation.
Maggiora
Marina
M
Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Corso Raffaello, Turin, Italy.
Oraldi
Manuela
M
Muzio
Giuliana
G
Canuto
Rosa Angela
RA
D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002994:Clofibrate / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D009994:Osmolar Concentration; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D054648:Protein Phosphatase 2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051025:bcl-Associated Death Protein / Q000378:metabolism
D008024:Ligands; C489427:MYC protein, human; D047493:PPAR alpha; D047495:PPAR gamma; D016271:Proto-Oncogene Proteins c-myc; D051025:bcl-Associated Death Protein; C037112:9-deoxy-delta-9-prostaglandin D2; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2; D002994:Clofibrate; D015230:Prostaglandin D2