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Lithium Enhances Autophagy and Cell Death in Skin Melanoma: An Ultrastructural and Immunohistochemical Study

Published online by Cambridge University Press:  20 May 2022

Iuliia Taskaeva Open the ORCID record for Iuliia Taskaeva [Opens in a new window] ,
Izabella Gogaeva Open the ORCID record for Izabella Gogaeva [Opens in a new window] ,
Anastasia Shatruk  and
Nataliya Bgatova Open the ORCID record for Nataliya Bgatova [Opens in a new window]
Iuliia Taskaeva*
Affiliation:
Laboratory 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, Timakova str. 2, 630060 Novosibirsk, Russia
Izabella Gogaeva
Affiliation:
Laboratory 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, Timakova str. 2, 630060 Novosibirsk, Russia
Anastasia Shatruk
Affiliation:
Laboratory 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, Timakova str. 2, 630060 Novosibirsk, Russia
Nataliya Bgatova
Affiliation:
Laboratory 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, Timakova str. 2, 630060 Novosibirsk, Russia
*
*Corresponding author: Iuliia Taskaeva, E-mail: [email protected]
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Abstract

Lithium is an inhibitor of glycogen synthase kinase 3 beta, which is traditionally used in the treatment of bipolar disorders and has antitumor effects. The aim of the current study was to determine if lithium salt causes autophagy and apoptosis in skin melanoma cells to enhance cell death. Light microscopy, transmission electron microscopy, immunohistochemistry, and immunofluorescence were used to study the mechanism of action of lithium carbonate in B16 melanoma cells in vivo. Proliferating cell nuclear antigen immunofluorescence assay revealed that the proliferation of B16 melanoma cells was suppressed by lithium treatment for 7 days. Electron microscopy demonstrated a significant increase in the number of autophagic vacuoles in lithium-treated cells relative to control. In addition, levels of autophagy markers LC3 beta and LAMP1 found in lithium-treated tumor xenografts were higher than levels of these markers in the control tumors. Lithium induced caspase-3 expression and apoptotic cell death in tumor cells. Thus, lithium carbonate is the compound that inhibits cell proliferation and stimulates cell death in melanoma cells through induction of autophagy and apoptosis. Stimulation of autophagy by lithium could contribute to the development of autophagic cell death in tumor cells.

Keywords

apoptosisautophagycell deathlithiumskin melanoma
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 28 , Issue 5 , October 2022 , pp. 1703 - 1711
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press on behalf of the Microscopy Society of America

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