Anti-tumor effects of epigallocatechin-3-gallate on head and neck cancer stem cells

Abstract

Most solid cancers including head and neck squamous cell carcinoma (HNSCC) are believed to be initiated from and maintained by cancer stem cells (CSCs) that are responsible for treatment resistance, resulting in tumor relapse. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, can potently inhibit cancer growth and induce apoptosis in various cancers, including HNSCC. However, its effect on HNSCC CSCs is not well elucidated. In this study, we examined the anti-tumor effect of EGCG on HNSCC CSCs. We demonstrated that EGCG inhibits the self-renewal capacity of HNSCC 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 gene, which are putative molecules of treatment resistance of CSC. In addition, the combination treatment of EGCG and cisplatin inhibited tumor formation and induced apoptosis in a xenograft model. As one of mechanism of suppression of HNSCC CSC traits, EGCG decreased the transcriptional level of Notch, resulting in inhibition of Notch signaling. Collectively, our data suggest that EGCG in combination with cisplatin can be used for the management of HNSCC CSCs