Does Scavenging of Mitochondrial Superoxide Attenuate Cancer Prosurvival Signaling Pathways? Научная публикация
| Журнал |
Antioxidants and Redox Signaling
ISSN: 1523-0864 , E-ISSN: 1557-7716 |
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| Вых. Данные | Год: 2013, Том: 19, Номер: 4, Страницы: 344-349 Страниц : DOI: 10.1089/ars.2013.5185 | ||||||
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Реферат:
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.
Библиографическая ссылка:
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
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
Файлы:
Полный текст от издателя
Даты:
| Опубликована в печати: | 1 авг. 2013 г. |
Идентификаторы БД:
| Web of science: | WOS:000321040700002 |
| Scopus: | 2-s2.0-84879860923 |
| РИНЦ: | 20439648 |
| OpenAlex: | W1968816740 |