Physalin A Induces Apoptosis and Autophagy in Hepatocellular Carcinoma via Inhibition of PI3K/Akt Signaling Pathway

Area of Science:

• Biochemistry
• Pharmacology
• Oncology

Background:

• Physalin A (PA) is a bioactive withanolide with demonstrated cytotoxic effects against hepatocellular carcinoma (HCC) cell line HepG2.
• Understanding the precise mechanisms of PA's antitumor activity in HCC is crucial for therapeutic development.

Purpose of the Study:

• To elucidate the molecular mechanisms by which Physalin A exerts its antitumor effects in hepatocellular carcinoma.
• To investigate the roles of apoptosis, autophagy, and the PI3K/Akt signaling pathway in PA's anti-HCC activity.

Main Methods:

• HepG2 cells were treated with varying concentrations of PA, and cell viability and apoptosis were assessed using CCK-8 assay and flow cytometry.
• Autophagy was detected via immunofluorescence staining for LC3, and protein levels related to autophagy, apoptosis, and PI3K/Akt signaling were measured by Western blotting.
• An in vivo xenograft mouse model was used to evaluate PA's antitumor efficacy.

Main Results:

• PA significantly reduced HepG2 cell viability and induced both apoptosis and autophagy.
• Inhibition of autophagy enhanced PA-induced apoptosis in HCC cells.
• PA suppressed PI3K/Akt signaling, and its activation reversed PA-mediated apoptosis and autophagy.
• PA treatment inhibited tumor growth in vivo.

Conclusions:

• Physalin A demonstrates significant antitumor activity against hepatocellular carcinoma.
• PA induces apoptosis and autophagy in HCC cells, partly through the inactivation of the PI3K/Akt signaling pathway.
• Targeting the PI3K/Akt pathway may be a key mechanism for PA's therapeutic effects in HCC.