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Abstract
Background: Hepatocellular carcinoma (HCC) is one of the most malignant cancers worldwide. The role of autophagy in the НСС development and progression is controversial and are still not well known. It has been shown that lithium induces autophagy and apoptosis, affects on proliferation and survival of various human malignancies. In this study we estimated lithium`s effects on autophagy in HCC in vivo.Materials and methods: Subcellular components and autophagic vacuoles were analyzed by transmission electron microscopy. The number of cells with LC3 and LAMP1 punctate was analyzed by double-immunofluorescence staining. Data are presented as mean ± standard deviation (SD). Mann–Whitney nonparametric tests were used to assess statistically significant differences at P < 0.05.Results: Lithium carbonate increased the numerical and volume density of autophagic vacuoles and autophagy marker LC3 beta. Therefore, lithium carbonate promotes enlarged autophagic vacuoles formation in HCC cells in vivo.Conclusion: Extended and unresolved autophagy induces cancer cell death by stimulating autophagic cell death. Thus, lithium-mediated autophagy can be an attractive approach in HCC chemotherapy.
Highlights
Autophagy is the process that allows cells to isolate and degrade subcellular components in lysosomes and/or vacuoles and subsequently process them for cell metabolism
autophagic cell death (ACD) is a form of cell death which characterized by the large-scale autophagic vacuolization of the cytoplasm [1] and several studies have suggested that extended and unresolved autophagy promotes cancer cell death by ACD [2,3]
The differences concerning the ultrastructural characteristics detected between control groups and lithium carbonate (LC) group regarded the structural polymorphism tumor cells (Figure 1, A)
Summary
Autophagy is the process that allows cells to isolate and degrade subcellular components in lysosomes and/or vacuoles and subsequently process them for cell metabolism. ACD is a form of cell death which characterized by the large-scale autophagic vacuolization of the cytoplasm [1] and several studies have suggested that extended and unresolved autophagy promotes cancer cell death by ACD [2,3]. Lithium induces autophagy and apoptosis, affects on proliferation and survival of tumor cells [12,13,14], and can ranks as an antitumor agent for HCC therapy. In this study we estimated lithiums effects on autophagy in HCC population in vivo. In this study we estimated lithiums effects on autophagy in HCC in vivo. Lithium carbonate promotes enlarged autophagic vacuoles formation in HCC cells in vivo. Conclusion: Extended and unresolved autophagy induces cancer cell death by stimulating autophagic cell death. Lithium-mediated autophagy can be an attractive approach in HCC chemotherapy
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