Ultrastructural Changes in Hepatocellular Carcinoma-29 Cells after Treatment with Lithium Carbonate

  • Yu. S. TaskaevaEmail author
  • N. P. Bgatova

We studied the effect of lithium carbonate on hepatocellular carcinoma-29 cells in CBA male mice after injection in a dose of 20 mM along the tumor periphery. Transmission electron microscopy revealed a decrease in the volume density of the granular endoplasmic reticulum in the cell cytoplasm and an increase in the total numerical and volume density of autophagosomes and autolysosomes and zones of destruction of intracellular organelles. The ability of lithium carbonate to activate intracellular degradation processes in tumor cells and to stimulate cell death can be used to develop new combined strategies in the chemotherapy for hepatocellular carcinoma.

Key Words

hepatocellular carcinoma lithium carbonate ultrastructural organization autophagy 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bgatova NP, Gavrilova YuS, Lykov AP, Solovieva AO, Makarova VV, Borodin YuI, Konenkov VI. Apoptosis and autophagy in hepatocarcinoma cells induced by different forms of lithium salts. Tsitologiya. 2017;59(3):178-184. Russian.Google Scholar
  2. 2.
    Gavrilova YuS, Bgatova NP, Solovieva AO, Trifonova KE, Lykov AP, Borodin YuI, Konenkov VI. The target cells of different lithium forms in heterogeneous population hepatocarcinoma-29. Tsitologiya. 2016;58(3):186-191. Russian.Google Scholar
  3. 3.
    Kaledin VI, Zhukova NA, Nikolin VP, Popova NA, Beliaev MD, Baginskaya NV, Litvinova EA, Tolstikova TG, Lushnikova EL, Semenov DE. Hepatocarcinoma-29, a metastasizing transplantable mouse tumor inducing cachexia. Bull. Exp. Biol. Med. 2009;148(6):903-908.CrossRefGoogle Scholar
  4. 4.
    Brito AF, Abrantes AM, Tralhão JG, Botelho MF. Targeting hepatocellular carcinoma: what did we discover so far? Oncol. Rev. 2016;10(2):302.CrossRefGoogle Scholar
  5. 5.
    Dash S, Chava S, Chandra PK, Aydin Y, Balart LA, Wu T. Autophagy in hepatocellular carcinomas: from pathophysiology to therapeutic response. Hepat. Med. 2016;8:9-20.CrossRefGoogle Scholar
  6. 6.
    Freland L, Beaulieu JM. Inhibition of GSK3 by lithium, from single molecules to signaling networks. Front. Mol. Neurosci. 2012;5:14. doi:
  7. 7.
    Liu L, Liao JZ, He X.X, Li PY. The role of autophagy in hepatocellular carcinoma: friend or foe. Oncotarget. 2017;8(34):57,707-57,722.Google Scholar
  8. 8.
    McCubrey JA, Steelman LS, Bertrand FE, Davis NM, Sokolosky M, Abrams SL, Montalto G, D’Assoro AB, Libra M, Nicoletti F, Maestro R, Basecke J, Rakus D, Gizak A, Demidenko ZN, Cocco L, Martelli AM, Cervello M. GSK-3 as potential target for therapeutic intervention in cancer. Oncotarget. 2014;5(10):2881-2911.CrossRefGoogle Scholar
  9. 9.
    Montella L, Palmieri G, Addeo R, Del Prete S. Hepatocellular carcinoma: Will novel targeted drugs really impact the next future? World J. Gastroenterol. 2016;22(27):6114-6126.CrossRefGoogle Scholar
  10. 10.
    Pietrocola F, Bravo-San Pedro J.M, Galluzzi L, Kroemer G. Autophagy in natural and therapy-driven anticancer immunosurveillance. Autophagy. 2017;13(12):2163-2170.CrossRefGoogle Scholar
  11. 11.
    Sade Y, Toker L, Kara NZ, Einat H, Rapoport S, Moechars D, Berry GT, Bersudsky Y, Agam G. IP3 accumulation and/or inositol depletion: two downstream lithium’s effects that may mediate its behavioral and cellular changes. Transl. Psychiatry. 2016;6(12):e968. doi: Scholar
  12. 12.
    Sarkar S, Floto RA, Berger Z, Imarisio S, Cordenier A, Pasco M, Cook LJ, Rubinsztein DC. Lithium induces autophagy by inhibiting inositol monophosphatase. J. Cell Biol. 2005;170(7):1101-1111.CrossRefGoogle Scholar
  13. 13.
    Vicencio JM, Ortiz C, Criollo A, Jones AW, Kepp O, Galluzzi L, Joza N, Vitale I, Morselli E, Tailler M, Castedo M, Maiuri M.C, Molgó J, Szabadkai G, Lavandero S, Kroemer G. The inositol 1,4,5-trisphosphate receptor regulates autophagy through its interaction with Beclin 1. Cell Death Differ. 2009;16(7):1006-1017.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Research Institute of Clinical and Experimental Lymphology — Affiliated Branch of Federal Research Center Institute of Cytology and GeneticsSiberian Division of the Russian Academy of SciencesSiberiaRussia
  2. 2.Novosibirsk National Research State UniversityNovosibirskRussia

Personalised recommendations