In Vitro Effects of Lithium Carbonate on Cell Cycle, Apoptosis, and Autophagy in Hepatocellular Carcinoma-29 Cells
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Bulletin of Experimental Biology and Medicine, Vol. 170, No. 2, December, 2020 ONCOLOGY
In Vitro Effects of Lithium Carbonate on Cell Cycle, Apoptosis, and Autophagy in Hepatocellular Carcinoma-29 Cells Y. S. Taskaeva1,2, N. P. Bgatova1, R. S. Dossymbekova3, A. O. Solovieva1, S. M. Miroshnichenko1,4, K. O. Sharipov5, and Z. B. Tungushbaeva3
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 8, pp. 221-226, August, 2020 Original article submitted March 31, 2020 We studied the effects of lithium carbonate on the cell cycle, apoptosis, and autophagy in hepatocellular carcinoma-29 cells (HCC-29) in vitro. Flow cytofluorometry analysis revealed accumulation of G2/M-phase HCC-29 cells and increase in the number of apoptotic cells in 48 h after administration of 5 mM lithium carbonate. Induction of autophagy in HCC-29 cells was detected by transmission electron microscopy and immunofluorescence staining. Thus, lithium carbonate produces an antitumor effect by arresting cell cycle in the G2/M-phase and induction of apoptosis and autophagy in HCC-29 cells, which confirms the lithium potential as a promising drug for the treatment of hepatocellular carcinoma. Key Words: hepatocellular carcinoma; lithium carbonate (Li2CO3); cell cycle; apoptosis; autophagy The problem of induction of cancer cell death is a topical trend in modern medical and biological research. Apoptosis, or programmed cell death, and cell cycle arrest are the two key processes associated with the mechanisms of action of the main antitumor drugs. Changes in the cell cycle regulation are considered a characteristic sign of tumor development, and blockade of these intracellular events is recognized as an effective strategy in the cancer therapy [9]. Autophagic cell death is a special type of programmed cell death and a promising target for enhancing antitumor therapy [7]. As autophagy can contribute to signaling cascades leading to apoptosis or autophagic death, it is important to study the possibility of its induction for more 1 Research Institute of Clinical and Experimental Lymphology — Affiliated Branch of Federal Research Centre Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia; 2Novosibirsk National Research State University, Novosibirsk, Russia; 3Abai Kazakh National Pedagogical University, Almaty, Republic of Kazakhstan; 4Research Institute of Biochemistry — Structural Subdivision of Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia; 5 S. D. Asfendiyarov Kazakh National Medical University, Almaty, Republic of Kazakhstan. Address for correspondence: inabrite@yandex. ru. I. S. Taskaeva
effective modulation of the mechanisms of tumor cell death. Complex relationships between autophagy and apoptosis are determined by participation of many apoptotic proteins in the autophagy signaling pathways [8]. For example, caspases 3 and 9 can cleave autophagy-associated proteins and the resulting fragments have different functional activi
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