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Jolkinolide B Induces Autophagy-Mediated Apoptosis through the Modulation of the PI3K/AKT/mTOR Pathway in Hepatoblastoma Cells
Vol 37, Issue 10, 2023
Abstract
Background: Hepatoblastoma (HB) is a common tumor in children, but there are few effective drugs against this tumor. Jolkinolide B (JB) has been found to inhibit tumorigenesis by inducing apoptosis in diverse cancer types. However, the effect of JB has not yet been reported in HB. The aim of this work was therefore to study the effect of JB on HB cells and the possible mechanism of action. Methods: The proliferative capacity of HB cells was determined with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and 5-Ethynyl-2′-deoxyuridine (EdU) assays. Transwell assay was employed to evaluate cell migration, while cell apoptosis was assessed by flow cytometry. The formation of autophagosomes was evaluated by calculating the number of green fluorescent protein-tagged LC3 (GFP-LC3) puncta. In addition, Western blot analysis was used to quantify the levels of cleaved-caspase-3, B-cell lymphoma-2 (Bcl-2)-Associated X (Bax), Bcl-2, sequestosome 1 (p62), microtubule associated protein 1 light chain 3 (LC3), phosphorylated protein kinase B (p-AKT) and p-mechanistic target of rapamycin kinase (mTOR). Results: JB treatment of HB cells decreased their viability and suppressed migration (p < 0.01). The administration of JB also increased apoptosis and autophagy in HB cells (p < 0.01). Interestingly, JB-induced apoptosis relied on the occurrence of autophagy. At the molecular level, JB decreased activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway, which further induced autophagy-mediated apoptosis (p < 0.01). Conclusion: JB inhibited the proliferation and migration of HB cells, and induced autophagy-dependent apoptosis at least partly by modulating PI3K/AKT/mTOR cascade signaling. These findings indicate that JB could be a potent compound for treating patients with HB.
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Copyright (c) 2023 Xiaohua Wang, Meng Jiang, Hui Lin, Shuyun Zheng, Weiling Wang, Fang Li, Shuying Li
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy