Paeonol induces cytoprotective autophagy via blocking the Akt/mTOR pathway in ovarian cancer cells

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Paeonol (Pae), derived from Moutan Cortex, exhibits anticancer properties.
• Autophagy modulation is a potential strategy for epithelial ovarian cancer treatment.
• The role of Pae in inducing autophagy and its impact on ovarian cancer remain unclear.

Purpose of the Study:

• To investigate whether Pae induces autophagy in ovarian cancer cells.
• To determine the relationship between Pae's anti-tumor effects and autophagy.
• To explore the underlying molecular mechanisms and therapeutic potential of combining Pae with autophagy inhibitors.

Main Methods:

• Assessing Pae's effects on cell proliferation, apoptosis, and autophagy in A2780 and SKOV3 ovarian cancer cells.
• Evaluating the synergistic effects of Pae combined with autophagy inhibitors (3-methyladenine, hydroxychloroquine) in vitro and in a xenograft model.
• Investigating the impact of Pae on the Akt/mTOR signaling pathway and its interaction with Akt and mTOR inhibitors (MK2206, rapamycin).

Main Results:

• Pae demonstrated antiproliferative and pro-apoptotic effects, alongside the induction of complete autophagic flux in ovarian cancer cells.
• Combination therapy with Pae and autophagy inhibitors showed synergistic anti-cancer activity with reduced side effects compared to cisplatin.
• Pae inhibited the Akt/mTOR pathway, and inhibiting Akt/mTOR further enhanced Pae-induced autophagy.

Conclusions:

• Autophagy induced by Pae plays a cytoprotective role in ovarian cancer cells.
• Pae inhibits the Akt/mTOR pathway, leading to cytoprotective autophagy.
• Combining Pae with autophagy inhibitors represents a promising therapeutic strategy for ovarian cancer by blocking Akt/mTOR-dependent autophagy.