Beta-phenylethyl isothiocyanate mediated apoptosis; contribution of Bax and the mitochondrial death pathway

The International Journal of Biochemistry & Cell Biology
P RoseM Whiteman

Abstract

The initiating events that lead to the induction of apoptosis mediated by the chemopreventative agent beta-phenyethyl isothiocyanate (PEITC) have yet to be elucidated. In the present investigation, we examined the effects of PEITC on mitochondrial function and apoptotic signaling in hepatoma HepG2 cells and isolated rat hepatocyte mitochondria. PEITC induced a conformational change in Bax leading to its translocation to mitochondria in HepG2 cells. Bax accumulation was associated with a rapid loss of mitochondrial membrane potential (Deltapsim), impaired respiratory chain enzymatic activity, release of mitochondrial cytochrome c and the activation of caspase-dependent cell death. Caspase inhibition did not prevent Bax translocation, the release of cytochrome c or the loss of Deltapsim, but blocked caspase-mediated DNA fragmentation and cell death. To determine whether PEITC dependent Bax translocation caused loss of Deltapsim by the activation of the mitochondrial permeability transition (MPT), we examined the effects of PEITC in isolated rat hepatocyte mitochondria. Interestingly, PEITC did not induce MPT in isolated rat mitochondria. Accordingly, using pharmacological inhibitors of MPT namely cyclosporine A, trifluoperazine a...Continue Reading

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Citations

Sep 1, 2005·Apoptosis : an International Journal on Programmed Cell Death·N Hail
Jan 31, 2006·The Proceedings of the Nutrition Society·Yuesheng ZhangJun Li
Dec 25, 2010·World Journal of Gastroenterology : WJG·Ji-Wu HanBao-Xin Li
May 6, 2008·Free Radical Biology & Medicine·Numsen HailJulian E Spallholz
Dec 17, 2008·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·Christopher D MannDavid P Berry
Jun 6, 2008·The Journal of Biological Chemistry·Lixin MiFung-Lung Chung
Apr 27, 2005·Journal of Bioinformatics and Computational Biology·Tho Hoan PhamTu Bao Ho
Jan 27, 2006·World Journal of Gastroenterology : WJG·Peter RoseMatt Whiteman
Aug 12, 2005·Molecular Cancer Therapeutics·Li Tang, Yuesheng Zhang
Mar 13, 2021·Free Radical Biology & Medicine·Qi Wang, Yongping Bao
Mar 2, 2006·Journal of Agricultural and Food Chemistry·Jana JakubíkováYongping Bao

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