Fenretinide induces mitochondrial ROS and inhibits the mitochondrial respiratory chain in neuroblastoma.

Cellular and Molecular Life Sciences : CMLS
Roos CuperusAndré B P van Kuilenburg

Abstract

Fenretinide induces apoptosis in neuroblastoma by induction of reactive oxygen species (ROS). In this study, we investigated the role of mitochondria in fenretinide-induced cytotoxicity and ROS production in six neuroblastoma cell lines. ROS induction by fenretinide was of mitochondrial origin, demonstrated by detection of superoxide with MitoSOX, the scavenging effect of the mitochondrial antioxidant MitoQ and reduced ROS production in cells without a functional mitochondrial respiratory chain (Rho zero cells). In digitonin-permeabilized cells, a fenretinide concentration-dependent decrease in ATP synthesis and substrate oxidation was observed, reflecting inhibition of the mitochondrial respiratory chain. However, inhibition of the mitochondrial respiratory chain was not required for ROS production. Co-incubation of fenretinide with inhibitors of different complexes of the respiratory chain suggested that fenretinide-induced ROS production occurred via complex II. The cytotoxicity of fenretinide was exerted through the generation of mitochondrial ROS and, at higher concentrations, also through inhibition of the mitochondrial respiratory chain.

References

Jan 17, 1985·The New England Journal of Medicine·J M McCord
Aug 17, 1994·Journal of the National Cancer Institute·A MariottiG Della Valle
Nov 1, 1995·Seminars in Surgical Oncology·J I Allen
Sep 30, 2000·Experimental Cell Research·P E LovatC P Redfern
Nov 28, 2000·International Journal of Cancer. Journal International Du Cancer·P E LovatC P Redfern
May 23, 2002·Biochimie·Andrew P HalestrapSamantha J Clarke
May 6, 2004·Annals of the New York Academy of Sciences·Yasuhito Nakagawa
Jan 15, 2005·Annals of the New York Academy of Sciences·Penny E LovatChristopher P F Redfern
May 24, 2005·Cancer Letters·Penny E LovatChristopher P F Redfern
Jun 1, 2005·Mechanisms of Ageing and Development·Andrew M JamesMichael P Murphy
Feb 26, 2008·The Biochemical Journal·Meredith F RossMichael P Murphy
Jun 14, 2008·Biochemical and Biophysical Research Communications·So Young EunHan Geuk Seo

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Citations

Jan 15, 2013·Cancer Chemotherapy and Pharmacology·Veena GaneshanNina F Schor
Dec 17, 2010·The Journal of Pharmacology and Experimental Therapeutics·Tanecia MitchellLee Ann MacMillan-Crow
Mar 21, 2012·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Aintzane ApraizAintzane Asumendi
Nov 7, 2013·International Journal of Molecular Sciences·Jie LiuXiao-Yan Xin
Nov 21, 2013·Cancer Chemotherapy and Pharmacology·Veena R Ganeshan, Nina F Schor
Apr 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Akiko MaedaKrzysztof Palczewski
Dec 22, 2011·Apoptosis : an International Journal on Programmed Cell Death·Jiin-Haur ChuangPei-Wen Wang
Jul 12, 2011·Free Radical Biology & Medicine·Roos CuperusGodelieve A M Tytgat
Feb 11, 2012·International Journal of Cancer. Journal International Du Cancer·Aleksandar BoroFelix K Niggli
Jul 14, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·Hao-Jie PuHiroshi Kurihara
Dec 24, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yaghoub SafdariSafar Farajnia
Mar 25, 2017·International Journal of Cancer. Journal International Du Cancer·Lluis Lopez-BarconsC Patrick Reynolds
Apr 12, 2013·Journal of Child Neurology·Nina F Schor
Oct 10, 2018·British Journal of Pharmacology·Li JiangBo Yang
Jun 23, 2011·Paediatric Drugs·Veena R Ganeshan, Nina F Schor
Mar 8, 2020·Cell Death and Differentiation·Eva BrackBeat W Schäfer
Jul 17, 2019·Current Medicinal Chemistry·Ioana MacasoiVictor Dumitrașcu
Aug 12, 2017·ACS Chemical Neuroscience·Jeanne N HansenNina F Schor
Jul 6, 2010·Mitochondrion·Rafael Moreno-SánchezHans V Westerhoff

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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