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Sidlauskas 2017 Neurosci Lett

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Sidlauskas K, Sidlauskiene R, Li N, Liobikas J (2017) 5-Hydroxy-1,4-naphthalenedione exerts anticancer effects on glioma cells through interaction with the mitochondrial electron transport chain. Neurosci Lett 639:207-14.

Β» PMID: 28069455

Sidlauskas K, Sidlauskiene R, Li N, Liobikas J (2017) Neurosci Lett

Abstract: Survival of patients with glioblastoma remains within the range of several months despite advances in therapeutic options. We have already shown that 5-hydroxy-1,4-naphthalenedione (juglone) exerts antiproliferative, anti-invasive, and cytotoxic effects on glioma C6 cells. Here, we further revealed that juglone is relatively selective to glioma cells as compared to the normal glial culture, and investigated its mechanisms of action. The incubation of glioma C6 cells with juglone generated high levels of reactive oxygen species (ROS). The produced ROS accounted for the anticancer effect of juglone as antioxidant N-acetylcysteine reduced both cytotoxic and antiproliferative activities of juglone. Furthermore, high-resolution respirometry revealed that juglone decreased oxygen consumption mainly by affecting pyruvate/malate- and glutamate/malate-induced mitochondrial respiration. The inhibition of respiratory complex I by amytal decreased juglone-triggered generation of ROS and diminished its anticancer activity. Thus, our results indicate that juglone generates ROS through interaction with respiratory complex I in glioma C6 cells, and, in turn, induces the anticancer effects.

Copyright Β© 2017 Elsevier B.V. All rights reserved. β€’ Keywords: Electron transport chain, Glioma, Juglone, Oxidative phosphorylation, Reactive oxygen species, C6 rat glioma cells β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: LT Kaunas Briedis V

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Cancer  Stress:Oxidative stress;RONS  Organism: Rat  Tissue;cell: Nervous system, Other cell lines  Preparation: Intact cells, Permeabilized cells 

Regulation: Inhibitor  Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, S  HRR: Oxygraph-2k