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Does Scavenging of Mitochondrial Superoxide Attenuate Cancer Prosurvival Signaling Pathways? Full article

Journal Antioxidants and Redox Signaling
ISSN: 1523-0864 , E-ISSN: 1557-7716
Output data Year: 2013, Volume: 19, Number: 4, Pages: 344-349 Pages count : DOI: 10.1089/ars.2013.5185
Authors Nazarewicz Rafal R. 1 , Dikalova Anna 1 , Bikineyeva Alfiya 1 , Ivanov Sergey 2 , Kirilyuk Igor A. 3 , Grigor'ev Igor A. 3 , Dikalov Sergey I. 1
Affiliations
1 (Данные Web of science) Vanderbilt Univ, Med Ctr, Div Clin Pharmacol, Nashville, TN 37232 USA
2 (Данные Web of science) Yale Canc Ctr, Dept Surg, New Haven, CT USA
3 (Данные Web of science) Novosibirsk Organ Chem Inst, Novosibirsk, Russia

Abstract: It has been previously suggested that overexpression of mitochondrial superoxide dismutase (SOD) attenuates cancer development; however, the exact mechanism remains unclear. In this work, we have studied the direct effect of the mitochondria-targeted superoxide scavenger, (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (mitoTEMPO), on B16-F0 mouse melanoma cells and tumor growth in a nude mouse model of human melanoma. We show that scavenging of mitochondrial superoxide inhibited cell growth, reduced viability, and induced apoptosis in melanoma cells, but did not affect nonmalignant skin fibroblasts. Diminished mitochondrial superoxide inhibited redox-dependent Akt, restored activity of mitochondrial pyruvate dehydrogenase, and reduced HIF1-alpha and lactate dehydrogenase expression in cancer cells. Suppression of glycolysis in mitoTEMPO-treated melanoma cells resulted in a significant drop of cellular adenosine-5'-triphosphate and induced cell death. In vivo mitoTEMPO treatment effectively suppressed growth of established tumor in the mouse model of human melanoma. Therefore, our data lead to the hypothesis that scavenging of mitochondrial superoxide selectively inhibits redox-sensitive survival and metabolic pathways, resulting in cancer cell death. In contrast to existing anticancer therapies, inhibition of mitochondrial superoxide may represent a novel specific anticancer treatment with reduced cytotoxic side effects.
Cite: Nazarewicz R.R. , Dikalova A. , Bikineyeva A. , Ivanov S. , Kirilyuk I.A. , Grigor'ev I.A. , Dikalov S.I.
Does Scavenging of Mitochondrial Superoxide Attenuate Cancer Prosurvival Signaling Pathways?
Antioxidants and Redox Signaling. 2013. V.19. N4. P.344-349. DOI: 10.1089/ars.2013.5185 WOS Scopus РИНЦ OpenAlex
Files: Full text from publisher
Dates:
Published print: Aug 1, 2013
Identifiers:
Web of science: WOS:000321040700002
Scopus: 2-s2.0-84879860923
Elibrary: 20439648
OpenAlex: W1968816740
Citing:
DB Citing
Web of science 70
Scopus 75
Elibrary 74
OpenAlex 89
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