title: Epigallocatechin-3-gallate attenuates head and neck cancer stem cell traits through suppression of Notch pathway.
abstract: Most solid cancers including head and neck squamous carcinoma (HNSC) are believed to be initiated from and maintained by cancer stem cells (CSCs) that are responsible for treatment resistance, resulting in tumour relapse. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, can potently inhibit cancer growth and induce apoptosis in various cancers, including HNSC. However, its effect on HNSC CSCs is not well elucidated. In this study, we examined the anti-tumour effect of EGCG on HNSC CSCs. We demonstrated that EGCG inhibits the self-renewal capacity of HNSC CSCs by suppressing their sphere forming capacity, and attenuates the expression of stem cell markers, such as Oct4, Sox2, Nanog and CD44. EGCG treatment augmented cisplatin-mediated chemosensitivity by suppressing ABCC2 and ABCG2 transporter genes, which are putative molecules of treatment resistance of CSC. In addition, the combination treatment of EGCG and cisplatin inhibited tumour formation and induced apoptosis in a xenograft model. As one of mechanisms of suppression of HNSC CSC traits, EGCG decreased the transcriptional level of Notch, resulting in the inhibition of Notch signalling. Collectively, our data suggest that EGCG in combination with cisplatin can be used for the management of HNSC CSCs.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Lee
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Nam
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kang
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Kwon
authors.forename: Young Chang
authors.initials: YC
authors.lastname: Lim
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000089762:Multidrug Resistance-Associated Protein 2; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C000715087:ABCC2 protein, human; D016588:Anticarcinogenic Agents; D000089762:Multidrug Resistance-Associated Protein 2; D051880:Receptors, Notch; D002392:Catechin; C045651:epigallocatechin gallate
keywords: Epigallocatechin-3-gallate; Head and neck cancer; Neoplastic stem cells; Notch; Therapy