Involvement of PPARs in Cell Proliferation and Apoptosis in Human Colon Cancer Specimens and in Normal and Cancer Cell Lines

PPAR involvement in cell growth was investigated "in vivo" and "in vitro" and was correlated with cell proliferation and apoptotic death. "In vivo" PPARgamma and alpha were evaluated in colon cancer specimens and adjacent nonneoplastic colonic mucosa. PPARgamma increased in most cancer specimens versus mucosa, with a decrease in c-Myc and in PCNA proteins, suggesting that colon cancer growth is due to increased cell survival rather than increased proliferation. The prevalence of survival over proliferation was confirmed by Bcl-2 or Bcl-X(L) increase in cancer versus mucosa, and by decreased PPARalpha. "In vitro" PPARgamma and PPARalpha were evaluated in human tumor and normal cell lines, treated with natural or synthetic ligands. PPARgamma was involved in inhibiting cell proliferation with a decrease in c-Myc protein, whereas PPARalpha was involved in inducing apoptosis with modulation of Bcl-2 and Bad proteins. This involvement was confirmed using specific antagonists of two PPARs. Moreover, the results obtained on treating cell lines with PPAR ligands confirm observations in colon cancer: there is an inverse correlation between PPARalpha and Bcl-2 and between PPARgamma and c-Myc.