Abstract
Physalin A (PA) is a bioactive withanolide with multiple pharmacological properties and has been indicated to be cytotoxic to hepatocellular carcinoma (HCC) cell line HepG2. This study aims to explore the mechanisms underlying PA antitumor activity in HCC. HepG2 cells were exposed to various concentrations of PA. Cell counting kit-8 assay and flow cytometry were implemented for evaluating cell viability and apoptosis, respectively. Immunofluorescence staining was utilized for detecting autophagic protein LC3. Western blotting was employed for measuring levels of autophagy-, apoptosis- and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling-related proteins. A xenograft mouse model was established to verify the antitumor activity of PA in vivo. PA impaired HepG2 cell viability, and triggered apoptosis as well as autophagy. Inhibiting autophagy augmented PA-evoked HepG2 cell apoptosis. PA repressed PI3K/Akt signaling in HCC cells and activating PI3K/Akt reversed PA-triggered apoptosis and autophagy. PA treatment inhibited tumor growth in tumor-bearing mice. PA triggers HCC cell apoptosis and autophagy by inactivating PI3K/Akt signaling.
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The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
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03 August 2023
A Correction to this paper has been published: https://doi.org/10.1007/s10528-023-10476-9
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This work was supported by the Youth Project of Medical Research Fund of Wuhan Municipal Health Commission (No.WX19Q15).
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XS and ZC conceived and designed the experiments. JXL, SGX, LBL, ZHY, YSC, PZR, XLP, XS and ZC carried out the experiments. XLP, XS and ZC analyzed the data. XLP, XS and ZC drafted the manuscript. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript.
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Shang, X., Chen, Z., Liu, J. et al. Physalin A Induces Apoptosis and Autophagy in Hepatocellular Carcinoma via Inhibition of PI3K/Akt Signaling Pathway. Biochem Genet 62, 633–644 (2024). https://doi.org/10.1007/s10528-023-10429-2
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DOI: https://doi.org/10.1007/s10528-023-10429-2