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Dependence of the Viability of Ras-Expressing Cells on Damage to Mitochondria Caused by Antitumor Agents

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Abstract

Tumors with ocogenic Ras protein expression are hard to cure, since they are able to restore viability after treatment with antitumor agents by activating cytoprotective processes. The search for new targets for more effective therapy has shown that mitochondria can serve as such a target, since Ras-expressing cells receive ATP primarily through oxidative phosphorylation, rather than glycolysis, like many other types of tumor cells. The study investigated the death of tumor cells expressing oncogenic Ras after X-ray irradiation in comparison with inhibitor of mitochondrial integrity ABT199 inhibitor (venetoclax) of mitochondrial integrity. It was shown that cells show different response in time to the action of damaging agents. In the early stages (2–24 h after of treatment), autophagy is activated, which eliminates damaged mitochondria and increases cell viability, while the appearance of senescent cells after 72 h is part of a late response that suppresses proliferation. Inhibition of autophagy and senescence increases cell death under the action of damaging agents, which indicates that these processes play a key role in inhibition of cell death after mitochondrial damage. Thus, inhibition of autophagy and senescence can increase the efficiency of tumor cell elimination by antitumor agents.

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Funding

This work was supported by budgetary funding from the Institute of Cytology, Russian Academy of Sciences.

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  1. Institute of Cytology, Russian Academy of Sciences, 194064, St. Petersburg, Russia

    E. Yu. Kochetkova, G. I. Blinova, A. S. Boytsov, V. A. Pospelov & T. V. Pospelova

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  1. E. Yu. Kochetkova
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  2. G. I. Blinova
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  3. A. S. Boytsov
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  4. V. A. Pospelov
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Correspondence to E. Yu. Kochetkova.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Kochetkova, E.Y., Blinova, G.I., Boytsov, A.S. et al. Dependence of the Viability of Ras-Expressing Cells on Damage to Mitochondria Caused by Antitumor Agents. Cell Tiss. Biol. 14, 437–447 (2020). https://doi.org/10.1134/S1990519X20060061

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  • DOI: https://doi.org/10.1134/S1990519X20060061

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