Bezafibrate Induces a Mitochondrial Derangement in Human Cell Lines. Intriguing Effects for a Peroxisome Proliferator.

Roberto Scatena, Giuseppina Nocca, Patrizia Bottoni, Federica Vincenzoni, Giuseppe Ettore Martorana, Pasquale De Sole, Nicola Giuseppe Maggiano, Massimo Castagnola, Bruno Giardina, Irene Messana

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Bezafibrate is a hypolipidemic drug that belongs to the group of peroxisome proliferators because it binds to peroxisome proliferator-activated receptors type alpha (PPARs). Peroxisome proliferators produce a myriad of extraperoxisomal effects, which are not necessarily dependent on their interaction with PPARs. An investigation on the peculiar activities of bezafibrate could clarify some of the molecular events and the relationship with the biochemical and pharmacological properties of this class of compounds. In this view, the human acute promyelocytic leukemia HL-60 cell line and human rabdomiosarcoma TE-671 cell line were cultured in media containing bezafibrate and a number of observations such as spectrophotometric analysis of mitochondrial respiratory chain enzymes, NMR metabolite determinations, phosphofructokinase enzymatic analysis, and differentiation assays were carried on. Bezafibrate induced a derangement of NADH cytochrome c reductase activity accompanied by metabolic alterations, mainly a shift to anaerobic glycolysis and an increase of fatty acid oxidation, as shown by NMR analysis of culture supernatants where acetate, lactate, and alanine levels increased. On the whole, the present results suggest a biochemical profile and a therapeutic role of this class of PPARs ligands more complex than those previously proposed.
Lingua originaleEnglish
pagine (da-a)1440-1447
Numero di pagine8
RivistaChemical Research in Toxicology
Stato di pubblicazionePubblicato - 2003

Keywords

  • atherosclerosis
  • cancer
  • diabetes
  • differentiation
  • metabolism

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