Immunoregulatory role of quercetin in lung cancer

Abstract Long-term nourishment with quercetin, a naturally occurring plant flavonoid abundant in citrus fruits, buckwheat, and onions, has been associated with reduced risks of chronic diseases, including cancer. In this study, we evaluated the therapeutic potential and the anti-cancer properties of quercetin in lung cancer using in vitro, in vivo, and ex vivo models. Quercetin induced tumor cell cycle arrest via the p53-p21 axis and suppressed tumor cell migration in both the A549 and H520 human lung cancer cell lines. Moreover, it reduced oxidative stress and downregulated the protein expression of oncogenic markers such as EGFR and PD-L1 on the surface of A549 cells in a dose-response manner. Quercetin significantly attenuated the proliferation and migration of the tumor cells. In an in vivo model, quercetin decreased the tumor load without affecting the body weight. In the ex vivo model, quercetin treatment resulted in the induction of interferon alpha-2 (IFN-α2), a well-known anti-tumor cytokine. These findings demonstrate that quercetin exerts potent anti-tumoral and anti- inflammatory effects in lung cancer by regulating cell cycle, oxidative stress, and immune pathways.