title: Quercetin induces growth arrest through activation of FOXO1 transcription factor in EGFR-overexpressing oral cancer cells.
abstract: The squamous cell carcinomas of the head and neck (SCCHNs) 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 to be antitumorigenesis, but the underlying mechanism remains 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 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 anticancer agent and that FOXO1 is crucial in quercetin-induced growth suppression in EGFR-overexpressing oral cancer.
authors.affiliation: Department of Nutrition, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Chun-Yin
authors.initials: CY
authors.lastname: Huang
authors.forename: Chien-Yi
authors.initials: CY
authors.lastname: Chan
authors.forename: I-Tai
authors.initials: IT
authors.lastname: Chou
authors.forename: Chia-Hsien
authors.initials: CH
authors.lastname: Lien
authors.forename: Hsiao-Chi
authors.initials: HC
authors.lastname: Hung
authors.forename: Ming-Fen
authors.initials: MF
authors.lastname: Lee
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D009062:Mouth Neoplasms / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D016588:Anticarcinogenic Agents; C085126:FOXO1 protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D014157:Transcription Factors; D011794:Quercetin; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt
keywords: EGFR; FOXO1; Oral cancer; Quercetin