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Cellular energetics as a target for tumor cell elimination

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Abstract

Investigation of cancer cell metabolism has revealed variability of the metabolic profiles among different types of tumors. According to the most classical model of cancer bioenergetics, malignant cells primarily use glycolysis as the major metabolic pathway and produce large quantities of lactate with suppressed oxidative phosphorylation even in the presence of ample oxygen. This is referred to as aerobic glycolysis, or the Warburg effect. However, a growing number of recent studies provide evidence that not all cancer cells depend on glycolysis, and, moreover, oxidative phosphorylation is essential for tumorigenesis. Thus, it is necessary to consider distinctive patterns of cancer metabolism in each specific case. Chemoresistance of cancer cells is associated with decreased sensitivity to different types of antitumor agents. Stimulation of apoptosis is a major strategy for elimination of cancer cells, and therefore activation of mitochondrial functions with direct impact on mitochondria to destabilize them appears to be an important approach to the induction of cell death. Consequently, the design of combination therapies using acclaimed cytotoxic agents directed to induction of apoptosis and metabolic agents affecting cancer cell bioenergetics are prospective strategies for antineoplastic therapy.

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Abbreviations

ANT:

adenine nucleotide translocase

α-TOS:

a-tocopheryl succinate

CypD:

cyclophilin D

DCA:

dichloroacetate

2-DG:

2-deoxyglucose

HIF:

hypoxia inducible factor

HK:

hexokinase

MOM(P):

mitochondrial outer membrane (permeabilization)

MPT(P):

mitochondrial permeability transition (pore)

OXPHOS:

oxidative phosphorylation

ROS:

reactive oxygen species

VDAC:

voltage-dependent anion channel.

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Authors and Affiliations

  1. Faculty of Basic Medicine, Lomonosov Moscow State University, 119991, Moscow, Russia

    P. V. Maximchik, A. V. Kulikov, B. D. Zhivotovsky & V. G. Gogvadze

  2. Institute of Environmental Medicine, Karolinska Institutet, Box 210, 17177, Stockholm, Sweden

    B. D. Zhivotovsky & V. G. Gogvadze

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  1. P. V. Maximchik
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  2. A. V. Kulikov
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  3. B. D. Zhivotovsky
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  4. V. G. Gogvadze
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Correspondence to V. G. Gogvadze.

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Published in Russian in Biokhimiya, 2016, Vol. 81, No. 2, pp. 147–165.

Originally published in Biochemistry (Moscow) On-Line Papers in Press as Manuscript BM15-173, December 27, 2015.

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Maximchik, P.V., Kulikov, A.V., Zhivotovsky, B.D. et al. Cellular energetics as a target for tumor cell elimination. Biochemistry Moscow 81, 65–79 (2016). https://doi.org/10.1134/S0006297916020012

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  • DOI: https://doi.org/10.1134/S0006297916020012

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