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Molecules 2016, 21(12), 1730; doi:10.3390/molecules21121730

The HK2 Dependent “Warburg Effect” and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate

1
Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego Street, 51-148 Wroclaw, Poland
2
KoDiscovery, LLC, UM BioPark, Suite 502 E&F, 801 West Baltimore Street, Baltimore, MD 21201, USA
3
Departments of Biological Chemistry and Oncology and member at large Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA
4
Institut des Sciences de la Vie, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium
*
Author to whom correspondence should be addressed.
Academic Editor: Jean Jacques Vanden Eynde
Received: 17 October 2016 / Revised: 9 December 2016 / Accepted: 11 December 2016 / Published: 15 December 2016
View Full-Text   |   Download PDF [725 KB, uploaded 15 December 2016]   |  

Abstract

This review summarizes the current state of knowledge about the metabolism of cancer cells, especially with respect to the “Warburg” and “Crabtree” effects. This work also summarizes two key discoveries, one of which relates to hexokinase-2 (HK2), a major player in both the “Warburg effect” and cancer cell immortalization. The second discovery relates to the finding that cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation. Also described are selected anticancer agents which generally act as strong energy blockers inside cancer cells. Among them, much attention has focused on 3-bromopyruvate (3BP). This small alkylating compound targets both the “Warburg effect”, i.e., elevated glycolysis even in the presence oxygen, as well as mitochondrial oxidative phosphorylation in cancer cells. Normal cells remain unharmed. 3BP rapidly kills cancer cells growing in tissue culture, eradicates tumors in animals, and prevents metastasis. In addition, properly formulated 3BP shows promise also as an effective anti-liver cancer agent in humans and is effective also toward cancers known as “multiple myeloma”. Finally, 3BP has been shown to significantly extend the life of a human patient for which no other options were available. Thus, it can be stated that 3BP is a very promising new anti-cancer agent in the process of undergoing clinical development. View Full-Text
Keywords: 3-bromopyruvate; antitumor therapy; Warburg effect; Crabtree effect; oxidative phosphorylation; glutathione; buthionine sulphoximine 3-bromopyruvate; antitumor therapy; Warburg effect; Crabtree effect; oxidative phosphorylation; glutathione; buthionine sulphoximine
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Lis, P.; Dyląg, M.; Niedźwiecka, K.; Ko, Y.H.; Pedersen, P.L.; Goffeau, A.; Ułaszewski, S. The HK2 Dependent “Warburg Effect” and Mitochondrial Oxidative Phosphorylation in Cancer: Targets for Effective Therapy with 3-Bromopyruvate. Molecules 2016, 21, 1730.

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