Ferroptosis Mediates the Anti-Cancer Effects of Quercetin by Inhibiting the LGR4/NF-κB/GPX4 Pathway in Oral Squamous Cell Carcinoma
By
Xiao-jiao Wang
Peng Zhang
Yue Gao
Yu Shao
Ling Chen
July 14, 2026
Objective: To examine whether quercetin induces ferroptosis in oral squamous cell carcinoma (OSCC) cells and explore the potential molecular mechanisms.
Approach: Gene manipulation: Studied the role of LGR4/NF-κB/GPX4 in OSCC cell lines CAL27 and SCC9 through gene overexpression or RNA interference.Quercetin treatment: Treated CAL27 and SCC9 OSCC cell lines with quercetin to examine its effects and underlying mechanisms.Key Findings: Quercetin reduced the viability of OSCC cells in a dose-dependent manner. Co-treatment with the ferroptosis inhibitor liproxstatin-1 counteracted quercetin-induced cell death. Quercetin decreased GPX4 expression by suppressing the LGR4/NF-κB signaling pathway. Interpretation: Ferroptosis may play a role in quercetin's anti-OSCC activity by blocking the LGR4/NF-κB/GPX4 axis.
Conclusion: Quercetin may induce ferroptosis in OSCC cells.