Quercetin induces growth arrest through transcription factor FOXO1 in EGFR‐overexpressing oral cancer

Abstract

The squamous cell carcinomas of the head and neck (SCCHN) with aberrant epidermal growth factor receptor (EGFR) signaling are often associated with poor prognosis and low survival. Therefore, efficient inhibition of the EGFR signaling could intervene with the development of malignancy. Quercetin appears anti‐tumorigenesis, but the underlying mechanism is unclear in oral cancer. Fork‐head box O (FOXO) transcription factors, Akt downstream effectors, are important regulators of cell growth. Here, we hypothesized that FOXO1 might be crucial in quercetin‐induced growth inhibition in EGFR‐overexpressing oral cancer. Quercetin treatment suppressed cell growth by inducing G2/M arrest and apoptosis in EGFR‐overexpressing HSC‐3 and TW206 oral cancer cells. 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. 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.This work was supported by the grants from China Medical University CMU97–303 and National Science Council NSC98–2320‐B‐039–021‐MY3