Quercetin induces ferroptosis by inactivating mTOR/S6KP70 pathway in oral squamous cell carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Oral squamous cell carcinoma (oSCC) is a prevalent cancer with limited therapeutic options.
• The anti-cancer mechanisms of quercetin, a flavonoid, are not fully understood in oSCC.
• Ferroptosis and the mTOR/S6KP70 pathway are implicated in cancer progression and treatment response.

Purpose of the Study:

• To investigate the effects of quercetin on ferroptosis in oSCC.
• To elucidate the role of the mTOR/S6KP70 signaling axis in quercetin-induced anti-cancer effects in oSCC.
• To explore quercetin as a potential therapeutic agent for oSCC.

Main Methods:

• oSCC cell lines were treated with quercetin.
• Cell viability was assessed using CCK-8 assays.
• Ferroptosis was measured by reactive oxygen species (ROS) and glutathione (GSH) levels.
• mTOR/S6KP70 axis activation was evaluated via Western blotting.
• Gene silencing and overexpression techniques were employed.

Main Results:

• Quercetin treatment significantly inhibited oSCC cell viability.
• Quercetin induced ferroptosis by increasing lipid peroxidation and decreasing GSH levels.
• This ferroptosis induction was dependent on the mTOR/S6KP70 pathway.
• Quercetin repressed SLC7A11 expression, a key regulator of ferroptosis.
• mTOR agonists and S6KP70 overexpression partially blocked quercetin's effects, while an mTOR inhibitor enhanced ferroptosis.

Conclusions:

• Ferroptosis is a novel anti-tumor mechanism of quercetin in oSCC.
• Quercetin exerts its anti-cancer effects by targeting the mTOR/S6KP70 cascade.
• Quercetin demonstrates potential as a therapeutic agent for oSCC by modulating ferroptosis and the mTOR/S6KP70 pathway.