Modulation of mitochondrial apoptosis by PI3K inhibitors

Mitochondrion
Simone Fulda

Abstract

Most anticancer therapies exert their action by triggering programmed cell death (apoptosis) in cancer cells. The mitochondrial pathway of apoptosis is initiated by mitochondrial outer membrane permeabilization, leading to the release of apoptogenic factors such as cytochrome c or Smac from the mitochondrial intermembrane space into the cytosol. Mitochondrial outer membrane permeabilization is tightly controlled, for example by pro- and anti-apoptotic proteins of the Bcl-2 family. Recent evidence indicates that inhibition of the PI3K/Akt/mTOR pathway by small-molecule PI3K inhibitors primes cancer cells to mitochondrial apoptosis by tipping the balance towards pro-apoptotic Bcl-2 proteins, resulting in increased mitochondrial outer membrane permeabilization. Thus, mitochondrial apoptotic events play an important role in PI3K inhibitor-mediated sensitization for apoptosis.

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Citations

Mar 5, 2016·Journal of Experimental & Clinical Cancer Research : CR·Min WangYan Li
Jan 16, 2016·BioMed Research International·Xian ZhangJianhe Gan
Jan 3, 2015·DNA and Cell Biology·Daniel WysokinskiJanusz Blasiak
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Dec 19, 2017·International Journal of Molecular Medicine·Ketao ZhangJianping Liu
Sep 8, 2020·Journal of Liposome Research·Yiying GuYunjun Liu
Aug 20, 2017·Environmental Health : a Global Access Science Source·Ellen WinckelmansKaren Vrijens
Jul 7, 2017·Cell & Bioscience·Xue-Ping JiangJiang-Feng Wu
Jun 15, 2019·Histochemistry and Cell Biology·Dongmei SuYunjun Zhou
Jun 12, 2020·Epilepsia Open·Pablo M Casillas-EspinosaTerence J O'Brien

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