Alpinetin Inhibits Oral Squamous Cell Carcinoma Proliferation via miR-211-5p Upregulation and Notch Pathway Deactivation

Abstract

Background: The effect of alpinetin (ALP) on miR-211-5p level and function in oral squamous cell carcinoma (OSCC) remains unclear.Materials and methods: Human OSCC cell lines (CAL-27 and TCA-8113) and a mouse xenograft model with subcutaneously injected TCA-8113 cells were used. Effect of ALP treatment on cell viability, cell cycle distributions, and p-p53, p21, c-PARP, cyclin D1, NICD, HES1, and miR-211-5p expression levels was analyzed. Influence of ALP on tumor volume and weight was determined.Results: ALP treatment (at doses 400 and 500 µM) significantly decreased the viability of CAL-27 and TCA-8113 cells (P < 0.05). It upregulated the number of cells in G1 phase and miR-211-5p expression, increased p-p53, p21, and c-PARP levels, and decreased cyclin D1 levels. Furthermore, miR-211-5p mimic treatment increased the number of cells in G1 phase, and p53, p21, and c-PARP levels, and decreased cyclin D1 levels. Contrasting effects were observed under anti-miR-211-5p treatment. ALP downregulated NICD and HES1, whereas anti-miR-211-5p increased NICD and HES1 expression. ALP effects were alleviated in both cell lines under Jagged-1 overexpression plasmid treatment. Finally, ALP inhibited tumor growth and increased miR-211-5p expression in vivo.Conclusion: ALP-induced miR-211-5p upregulation and Notch pathway deactivation may be involved in its anti-proliferative effects in OSCC.