Bisphenol A diglycidyl ether-induced apoptosis involves Bax/Bid-dependent mitochondrial release of apoptosis-inducing factor (AIF), cytochrome c and Smac/DIABLO

British Journal of Pharmacology
Sebastian FehlbergRüdiger Göke

Abstract

(1) Bisphenol A diglycidyl ether (BADGE) is a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) antagonist, which is able to induce apoptosis in tumor cells independently of PPAR-gamma in caspase-dependent and -independent manners. Additionally, BADGE promotes TRAIL-induced apoptosis. (2) We report that BADGE activates via Bax and caspases-2 and -8 both the intrinsic and extrinsic apoptotic pathways using Bid as a shunt. (3) BADGE stimulates the mitochondrial release of apoptosis-inducing factor (AIF), cytochrome c and second mitochondria-derived activator of caspase/direct IAP-binding protein with low pl (Smac/DIABLO). The release of cytochrome c could not be blocked by inhibitors of caspases-3, -8 and -9 indicating that BADGE acts upstream of caspases-3 and -9 and does not involve caspase-8 to release cytochrome c. (4) While the caspase-independent apoptotic effect might be mediated by AIF, the sensitizing effect of BADGE against other apoptotic substances is most likely mediated by the X-linked inhibitor of apoptosis inhibitor Smac/DIABLO. (5) Our data suggest that BADGE or BADGE derivatives could represent promising substances for the treatment of neoplasms improving the antitumoral activity of TRAIL.

References

Jan 1, 1995·Molecular and Cellular Biology·P TontonozB M Spiegelman
May 15, 1994·Genes & Development·P TontonozB M Spiegelman
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·J M JürgensmeierJ C Reed
Jun 1, 2000·Cellular Immunology·R GökeY Chen
Oct 13, 2000·British Journal of Pharmacology·D Bishop-BaileyT D Warner
Dec 21, 2000·Trends in Pharmacological Sciences·G J Murphy, J C Holder
Nov 21, 2001·Nature Cell Biology·K F Ferri, G Kroemer
Jan 10, 2002·Genes & Development·Yibin DengXiangwei Wu
Feb 8, 2002·The Journal of Biological Chemistry·Yin GuoEmad S Alnemri
Apr 10, 2002·The Journal of Biological Chemistry·Youngsoo KimJohn C Reed

❮ Previous
Next ❯

Citations

Apr 26, 2008·Apoptosis : an International Journal on Programmed Cell Death·Lilian SewingRüdiger Göke
Aug 30, 2012·Nature Communications·Natsumaro KutsunaSeiichiro Hasezawa
Jun 28, 2007·Expert Opinion on Investigational Drugs·Katherine L Schaefer
Oct 30, 2012·Dental Materials : Official Publication of the Academy of Dental Materials·Dimitrios KloukosGeorge Eliades
May 30, 2008·PPAR Research·Katherine L Schaefer
Aug 4, 2009·Journal of Zhejiang University. Science. B·Mei-xiang XiangChun Gui
May 24, 2015·Dental Materials : Official Publication of the Academy of Dental Materials·Dimitrios KloukosTheodore Eliades
Oct 30, 2016·Reproductive Toxicology·Arcangelo BarbonettiFelice Francavilla
Apr 23, 2019·Chemical Biology & Drug Design·Lea M StitzleinRichard W Dudley
Feb 21, 2008·Journal of Agricultural and Food Chemistry·Jun YonekuboJunko Sajiki

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis