Redox Modulation in Therapy of Cancer: Some Pros and Cons

Zorova, Ljubava D.; Semenovich, Dmitry S.; Zorov, Savva D.; Oleynikov, Ilya P.; Kargapoltceva, Anastasia S.; Prutskikh, Dmitry V.; Abramicheva, Polina A.; Pevzner, Irina B.; Sukhikh, Gennady T.; Zorov, Dmitry B.

doi:10.3390/antiox14121496

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Redox Modulation in Therapy of Cancer: Some Pros and Cons

by

Ljubava D. Zorova

^1,2,*

,

Dmitry S. Semenovich

^1,2

,

Savva D. Zorov

¹,

Ilya P. Oleynikov

¹,

Anastasia S. Kargapoltceva

³,

Dmitry V. Prutskikh

⁴

,

Polina A. Abramicheva

¹

,

Irina B. Pevzner

^1,2

,

Gennady T. Sukhikh

² and

Dmitry B. Zorov

^1,2,*

¹

A.N. Belozersky Research Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, 119991 Moscow, Russia

²

V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 117997 Moscow, Russia

³

Biological Faculty, M.V. Lomonosov Moscow State University, 119991 Moscow, Russia

⁴

Research Institute of Molecular and Cellular Medicine, RUDN University, 117198 Moscow, Russia

^*

Authors to whom correspondence should be addressed.

Antioxidants 2025, 14(12), 1496; https://doi.org/10.3390/antiox14121496

Submission received: 27 November 2025 / Accepted: 7 December 2025 / Published: 12 December 2025

(This article belongs to the Special Issue Redox Signaling in Cancer: Mechanisms and Therapeutic Opportunities)

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Abstract

Redox potential controls a vast array of biochemical reactions, and its changes influence the transition from normal to pathological states. However, cellular redox potential is primarily assessed after extraction of water-soluble components (reduced and oxidized) from biological material, particularly glutathione, which, due to its abundance, determines intracellular redox potential. This process involves mechanistic averaging of redox potential values across tissue or cell, although existing data suggest, and sometimes directly indicate, heterogeneity in redox potential both within cells and within tissue. We argue that mitochondria determine cellular redox state, in particular through changes in the state of the mitochondrial reticulum caused by various internal and external factors. We describe the possibilities for regulation of redox status of the cell and organ as a potential therapy for various pathologies, particularly cancer, and propose intensifying efforts to utilize intrinsic redox indicators. We specifically examine the possibility of changes the redox potential in cancer cells through the use of oxidative phosphorylation uncouplers and propose mechanisms by which cancer cells may be killed using uncouplers. Particular attention is paid to the mitochondrial membrane potential as a powerful regulator of cellular metabolism, possibly unrelated to the regulation of reactive oxygen species levels, with the possible existence of a membrane potential sensor in cells.

Keywords: cancer; mitochondria; redox potential; glutathione; NADH; NAD; uncouplers; uncoupling; reticulum; fragmentation; membrane potential; sensor

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MDPI and ACS Style

Zorova, L.D.; Semenovich, D.S.; Zorov, S.D.; Oleynikov, I.P.; Kargapoltceva, A.S.; Prutskikh, D.V.; Abramicheva, P.A.; Pevzner, I.B.; Sukhikh, G.T.; Zorov, D.B. Redox Modulation in Therapy of Cancer: Some Pros and Cons. Antioxidants 2025, 14, 1496. https://doi.org/10.3390/antiox14121496

AMA Style

Zorova LD, Semenovich DS, Zorov SD, Oleynikov IP, Kargapoltceva AS, Prutskikh DV, Abramicheva PA, Pevzner IB, Sukhikh GT, Zorov DB. Redox Modulation in Therapy of Cancer: Some Pros and Cons. Antioxidants. 2025; 14(12):1496. https://doi.org/10.3390/antiox14121496

Chicago/Turabian Style

Zorova, Ljubava D., Dmitry S. Semenovich, Savva D. Zorov, Ilya P. Oleynikov, Anastasia S. Kargapoltceva, Dmitry V. Prutskikh, Polina A. Abramicheva, Irina B. Pevzner, Gennady T. Sukhikh, and Dmitry B. Zorov. 2025. "Redox Modulation in Therapy of Cancer: Some Pros and Cons" Antioxidants 14, no. 12: 1496. https://doi.org/10.3390/antiox14121496

APA Style

Zorova, L. D., Semenovich, D. S., Zorov, S. D., Oleynikov, I. P., Kargapoltceva, A. S., Prutskikh, D. V., Abramicheva, P. A., Pevzner, I. B., Sukhikh, G. T., & Zorov, D. B. (2025). Redox Modulation in Therapy of Cancer: Some Pros and Cons. Antioxidants, 14(12), 1496. https://doi.org/10.3390/antiox14121496

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