Emodin-induced autophagy against cell apoptosis through the PI3K/AKT/mTOR pathway in human hepatocytes
| Autor: | Rong Zhang, Shi-wen Zhou, Shi-Ming Yang, Su-min Wang, Guobing Li, Xiao-yuan Zheng |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pharmacology Chemistry Autophagy Pharmaceutical Science 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Cell culture Apoptosis Annexin 030220 oncology & carcinogenesis Drug Discovery Hepatic stellate cell Cancer research Emodin Protein kinase B PI3K/AKT/mTOR pathway |
| Zdroj: | Drug Design, Development and Therapy. 13:3171-3180 |
| ISSN: | 1177-8881 |
| Popis: | Background Emodin, a major component of Polygonum multiflorum (PM), has been reported to exert both protective and toxic effects in several cell types. However, the effects and underlying mechanisms of action of emodin in hepatic cells are still obscure. Methods The present study used the normal human liver cell line L02 to investigate the effects and mechanisms of emodin in hepatic cells. After treatment with emodin, L02 cells were examined for viability, apoptosis and autophagy with the Cell Counting Kit-8 (CCK-8), annexin V/PerCP staining and GFP-LC3 plasmid transfection. The expression of proteins including cleaved caspase-3, LC3B-I/II, p-PI3K, PI3K, p-AKT, AKT, p-mTOR, mTOR and actin was examined by using Western blot. Results Emodin significantly inhibited the viability of and induced apoptosis in L02 cells in a dose- and time-dependent manner. In addition, emodin increased the number of GFP-LC3 puncta in L02 cells and upregulated the expression of LC3B-II compared to those in control cells. Furthermore, emodin significantly decreased the expression of p-PI3K, p-AKT and p-mTOR in a dose-dependent manner compared to that in control cells without altering the expression of PI3K, AKT and mTOR. Notably, cotreatment with emodin and 3-methyladenine (3-MA) or rapamycin significantly increased and decreased the apoptosis rate of L02 cells, respectively, compared to that of cells treated with emodin alone. Conclusion In conclusion, emodin exhibited cytotoxicity in the L02 human hepatic cell line by promoting apoptosis, and it also induced autophagy through the suppression of the PI3K/AKT/mTOR signalling pathway. The autophagy could play a protective role following emodin treatment. |
| Databáze: | OpenAIRE |
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