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 induc e apoptosis in tumor cells. As mitochondria play a pivotal role in the indu ction of the apoptotic process, we analyzed the effect of curcumin on mitoc hondrial function. Curcumin induced an increase in rat liver mitochondrial membrane permeability, resulting in swelling, loss of membrane potential an d inhibition of ATP synthesis, These effects were mediated by the opening o f the permeability transition pore. Curcumin pore induction involved the ox idation of membrane thiol functions and required the presence of low Ca2+ c oncentrations. These data suggest that mitochondria might be a target by wh ich curcumin induces apoptosis of tumor cells. (C) 2001 Federation of Europ ean Biochemical Societies. Published by Elsevier Science B.V, All rights re served.