The lithium effects on morphology and apoptosis in hepatocellular carcinoma cells

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Iuliia Taskaeva¹, Izabella Gogaeva², Natalia Obanina³, Viktoriia Makarova⁴, Nataliya Bgatova^5
1Laboratory of ultrastructural research, Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Laboratory of boron-neutron capture therapy, Department of Physics, Novosibirsk State University, inabrite@yandex.ru
²Laboratory of ultrastructural research, Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Department of Natural Sciences, Novosibirsk State University, i.gogaeva@g.nsu.ru
³Laboratory of ultrastructural research, Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences; Section of cytology and genetics, Department of Natural Sciences, Novosibirsk State University, n.obanina@g.nsu.ru
⁴Laboratory of ultrastructural research, Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, shedina_vika@mail.ru
⁵Laboratory of ultrastructural research, Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, n_bgatova@ngs.ru

Hepatocellular carcinoma (HCC) is characterized dysregulation of cell death mechanisms, and the imbalance of pro- and anti-apoptotic signals. The development of HCC is accompanied by genetic mutations in the signaling pathways involved in the cell proliferation, growth and death. The molecular changes in apoptosis signaling in HCC determine the requirement for targeted chemotherapy to increasing apoptosis in HCC cells. The aim of this study was to assess the ability of lithium to influence on the hepatocellular carcinoma-29 (HCC-29) cells apoptosis in vivo. Light and transmission electron microscopy, and immunofluorescence staining were used to evaluate of apoptosis development in HCC-29 cells after administration of 20 mM lithium carbonate. It was revealed that lithium extremely increased the pro-apoptotic proteins Bad and caspase-3 expression, and decreased the anti-apoptotic protein Bcl-2 expression. These results indicate that lithium carbonate induces apoptosis pathways in HCC-29 cells. Lithium administration can enhance pro-apoptotic chemotherapeutic drugs potential and overcome the resistance of tumor cells to apoptosis in HCC.