The NADH-fumarate reductase system, a novel mitochondrial energy metabolism, is a new target for anticancer therapy in tumor microenvironments

Annals of the New York Academy of Sciences
Eriko TomitsukaHiroyasu Esumi

Abstract

Since deficiencies of critical nutrients and hypoxia are observed in hypovascular tumors, glycolysis alone cannot explain how cancer cells maintain their required energy levels. To study energy metabolism in cancer cells within such tumor microenvironments, we examined the NADH-fumarate reductase system, which is found in anaerobic organisms, such as parasitic helminthes. In human cancer cells cultured under tumor microenvironment-mimicking conditions, mitochondrial NADH-fumarate reductase activity increased in parallel with an increase in fumarate reductase activity, which is the reverse reaction of succinate-ubiquinone reductase and is regulated by the phosphorylation of its subunit. Pyrvinium pamoate, an anthelmintic drug, has an anticancer effect within tumor-mimicking microenvironments. We found that one of the biological mechanisms of pyrvinium is the inhibition of the NADH-fumarate reductase system. Therefore, the NADH-fumarate reductase system might be important for maintaining mitochondrial energy metabolism within the tumor microenvironments and might represent a novel target for anticancer therapies.

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Citations

Apr 25, 2012·Cell Research·José Manuel Rodríguez-VargasF Javier Oliver
Mar 9, 2013·PloS One·Clare B EdwardsPatrick C Bradshaw
Jul 26, 2014·International Journal of Colorectal Disease·Armin WiegeringChristoph Otto
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Nov 19, 2015·International Journal of Molecular Sciences·Xiaonan ZhangStig Linder
Jan 3, 2013·Cancer Science·Tomoyoshi Soga
Jun 15, 2014·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Tamaki OgawaNobuhiro Takahashi
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Jun 13, 2020·Frontiers in Oncology·Marija Vlaski-LafargeZoran Ivanovic
Aug 9, 2019·The International Journal of Biochemistry & Cell Biology·Christos Chinopoulos

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