An Unusual Pathway of Mitoptosis Found in Ehrlich Carcinoma Cells
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RAL BIOLOGY
An Unusual Pathway of Mitoptosis Found in Ehrlich Carcinoma Cells E. A. Pimenovaa,*, Yu. A. Reunovaa, E. S. Menchinskayab, A. A. Reunova,c, and Corresponding Member of the RAS D. L. Amininb,d Received May 22, 2020; revised June 7, 2020; accepted June 9, 2020
Abstract—An integrated microscopic study of the destruction of mouse Ehrlich ascites carcinoma (EAC) cells under starvation conditions has been carried out. It has been found that, in addition to apoptosis, necrosis, and apoptotic necrosis, already known for EAC, cell destruction can also occur through mitochondrial autolysis, which is proposed to be considered a new kind of mitoptosis. A mitoptosis in EAC is characterized by the appearance of many autolyzing mitochondria, the fusion of which leads to rupture of the cell membrane and the ejection of the nucleus from the cell. It is assumed that the polymorphism of EAC destruction patterns is explained by the different physiological state of the cells, which determines the “choice” of the cell death mechanism. This situation poses a challenge for researchers to develop complex inducers with the ability to stimulate all possible types of cancer cell death.
Keywords: mouse Ehrlich ascites carcinoma, mitochondria, mitoptosis DOI: 10.1134/S0012496620050063
Today, the study of the mechanisms of cancer cells destruction is the subject of increased attention due to the need in invention of effective anti-tumor inducers [1–7]. Mouse Ehrlich ascytic carcinoma (EAC) has a relatively high sensitivity to therapeutic effects, which makes it a convenient model for studying various aspects of programmed death [8–10]. Both apoptosis and necrosis were revealed in a study of the cells destruction under the same culture conditions of monolayer EAC [11]. In addition, a third pattern of cell death was found, corresponding to the morphological model of apoptotic necrosis [12]. It has been shown that a shift towards necrosis can be achieved with the use of the anti-tumor inducer cucumarioside A2-2 [12], the use of which activates cytoplasmic and a A.V.
Zhirmunsky National Scientific Centre of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, Vladivostok, 690041 Russia b G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of Russian Academy of Sciences, Vladivostok, 690022 Russia c St. Francis Xavier University, Antigonish NS B2G 2W5, Nova Scotia, Canada d Kaohsiung Medical University, Kaohsiung, Taiwan 807 *e-mail: [email protected]
nuclear autolysis, which occurs during active expression of calpain and caspase-1 [7]. Our study was carried out on EAC cells under imitation of starvation. It has been found that cell destruction can also occur in a previously unknown way, in which gradual fusion of vacuolated mitochondria leads to rupture of the cell membrane and the release of the cell nucleus into the intercellular space. We interpret this variant of cell death as a previously unknown type of mitoptosis, which we conditionally characterize as “catastrophic mitoptosis.” Identifica
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