| Summary: | 碩士 === 中國醫藥大學 === 營養學系碩士班 === 100 === Oral cancer is one of the most common head and neck cancers. It generally has a poor prognosis due to its frequent lymph node metastasis and local invasion. Recently, the use of natural compounds with low toxicity to prevent or treat cancers has gained tremendus interest. Quercetin, a major dietary flavonoid present in various plants, has potent anticancer activity, but the underlying mechanism in oral cancer is unclear. Mammalian forkhead box O (FOXO) transcription factors, including FOXO1, FOXO3a, FOXO4, FOXO6, are implicated in the regulation of several biological processes, including cell cycle, apoptosis and DNA repair. In this study, we hypothesized that FOXOs function as critical regulator in quercetin-mediated growth inhibition and migration in oral cancers. Our results showed that quercetin dose-dependently suppressed cell growth by inducing G2 arrest and apoptosis in EGFR-overexpressing HSC-3 and TW206 oral cancer cells. In addition, quercetin inhibited EGFR/Akt activation with a concomitant induction of FOXO1 activation. FOXO1-knockdown attenuated quercetin-induced p21 and FasL expression and subsequent G2 arrest and apoptosis, respectively. Likewise, quercetin suppressed tumor growth in HSC- 3 xenograft mice. Furthermore, quercetin-mediated suppression in cell migration is also FOXO1-dependent. Taken together, our data indicate that quercetin is an effective anti-cancer agent and that FOXO1 is crucial in quercetin-induced growth suppression in EGFR-overexpressing oral cancer.
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