Curcumin induces the mitochondrial permeability transition pore mediated by membrane protein thiol oxidation.
Curcumin is a natural compound showing antiproliferative properties. Recent studies suggest that these properties might be due to its ability to induce apoptosis in tumor cells. As mitochondria play a pivotal role in the induction of the apoptotic process, we analyzed the effect of curcumin on mitochondrial function. Curcumin induced an increase in rat liver mitochondrial membrane permeability, resulting in swelling, loss of membrane potential and inhibition of ATP synthesis. These effects were mediated by the opening of the permeability transition pore. Curcumin pore induction involved the oxidation of membrane thiol functions and required the presence of low Ca(2+) concentrations. These data suggest that mitochondria might be a target by which curcumin induces apoptosis of tumor cells.
Morin
D
D
Laboratoire de Pharmacologie, Faculté de Médecine, Créteil, France. morin@univ-paris12.fr
Barthélémy
S
S
Zini
R
R
Labidalle
S
S
Tillement
J P
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels; D008027:Light; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins / Q000187:drug effects* / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D008933:Mitochondrial Swelling / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012542:Scattering, Radiation; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D000970:Antineoplastic Agents; D002614:Chelating Agents; D007473:Ion Channels; D008565:Membrane Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D003474:Curcumin; D002118:Calcium