Manganese (III) meso-tetrakis N-ethylpyridinium-2-yl porphyrin acts as a pro-oxidant to inhibit electron transport chain proteins, modulate bioenergetics, and enhance the response to chemotherapy in lymphoma cells

Free Radical Biology & Medicine
Melba C JaramilloMargaret E Tome

Abstract

The manganese porphyrin, manganese (III) meso-tetrakis N-ethylpyridinium-2-yl porphyrin (MnTE-2-PyP(5+)), acts as a pro-oxidant in the presence of intracellular H2O2. Mitochondria are the most prominent source of intracellular ROS and important regulators of the intrinsic apoptotic pathway. Due to the increased oxidants near and within the mitochondria, we hypothesized that the mitochondria are a target of the pro-oxidative activity of MnTE-2-PyP(5+) and that we could exploit this effect to enhance the chemotherapeutic response in lymphoma. In this study, we demonstrate that MnTE-2-PyP(5+) modulates the mitochondrial redox environment and sensitizes lymphoma cells to antilymphoma chemotherapeutics. MnTE-2-PyP(5+) increased dexamethasone-induced mitochondrial ROS and oxidation of the mitochondrial glutathione pool in lymphoma cells. The combination treatment induced glutathionylation of Complexes I, III, and IV in the electron transport chain, and decreased the activity of Complexes I and III, but not the activity of Complex IV. Treatment with the porphyrin and dexamethasone also decreased cellular ATP levels. Rho(0) malignant T-cells with impaired mitochondrial electron transport chain function were less sensitive to the combin...Continue Reading

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Citations

Oct 27, 2015·Free Radical Biology & Medicine·Artak TovmasyanInes Batinic-Haberle
Feb 10, 2016·Antioxidants & Redox Signaling·Ines Batinic-HaberleIvan Spasojevic
Mar 31, 2017·Antioxidants & Redox Signaling·Sung-Won ShinWon Park
May 19, 2017·Radiation Research·Samuel R BirerKathleen A Ashcraft
Jan 13, 2018·Antioxidants & Redox Signaling·Luksana ChaiswingDaret K St Clair
Jul 8, 2017·Cancer Chemotherapy and Pharmacology·M K BossI Spasojevic
May 28, 2019·Redox Biology·Ines Batinic-Haberle, Margaret E Tome
Apr 6, 2021·Oxidative Medicine and Cellular Longevity·Ines Batinic-HaberleAngeles Alvarez Secord
Jul 2, 2021·Nature Reviews. Drug Discovery·Henry Jay Forman, Hongqiao Zhang

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