Inhibition of Mitochondrial Complex II by the Anticancer Agent Lonidamine.
Bottom Line: However, the effect of LND on central energy metabolism has never been fully characterized.The ability of LND to promote cell death was potentiated by its suppression of the pentose phosphate pathway, which resulted in inhibition of NADPH and glutathione generation.Using stable isotope tracers in combination with isotopologue analysis, we showed that LND increased glutaminolysis but decreased reductive carboxylation of glutamine-derived α-ketoglutarate.
Affiliation: From the Penn Superfund Research and Training Program Center, Center of Excellence in Environmental Toxicology, and Department of Systems Pharmacology and Translational Therapeutics and.Show MeSH
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Mentions: As part of the ETC, complex II is also a source of ROS. It mainly produces ROS from either the reduced FAD or ubiquinone site when downstream components of the ETC are blocked (40, 41). To examine whether LND induces intracellular ROS generation, we quantified the level of ROS by 2′,7′-dichlorofluorescein fluorescence (Fig. 4, A–C). Surprisingly, the level of ROS formed in LND-treated cells was even higher than the level in cells treated with TTFA (Fig. 4, A and C).
Affiliation: From the Penn Superfund Research and Training Program Center, Center of Excellence in Environmental Toxicology, and Department of Systems Pharmacology and Translational Therapeutics and.