Grape Seed Polyphenols Inhibit Proliferation and Migration of Oral Squamous Cell Carcinoma Cells Via Reduced Glycolysis and Cell Cycle Arrest
Objective To elucidate the effects of grape seed polyphenols(GSP)on the proliferation,migration,cell cycle,and glycolysis of human oral squamous cell carcinoma(OSCC)cells and its underlying mechanisms.Methods Oral squamous cell carcinoma cell lines(HN6 and Ca127)were treated with GSP at concentrations of 3,6,12,24,and 48 μg·mL-1;cell proliferation was evaluated using the CCK8 assay,while cell migration was assessed via the scratch assay;flow cytometry was employed to analyze cell cycle progression;glucose concentrations in the cell supernatant were quantified using the glucose oxidase method;pyruvate and lactate concentrations were determined through colorimetric assays;the expression levels of genes associated with cell proliferation,migration,and cell cycle were measured using RT-qPCR.Results GSP demonstrated a significant inhibitory effect on the proliferation and migration of HN6 and Ca127 cell lines within the concentration range of 6 to 48 μg·mL-1,exhibiting a dose-dependent relationship(P<0.05 or P<0.01).Treatment with GSP induced cell cycle arrest in the G1 phase in HN6 cells and in the G2 phase in Ca127 cells.Compared to the control group,the GSP-treated group exhibited a significant reduction in glucose uptake,pyruvate production,and lactate production in OSCC cells(P<0.01).Furthermore,GSP treatment resulted in a significant downregulation of the expression levels of genes associated with tumor cell proliferation(MKi67,MYC,PCNA),migration(CDH2,Twist,Slug),and cell cycle(CyclinDl,CDK4,CDK6,CyclinB2,CDK1)compared to the control group(P<0.01).Conclusions GSP can inhibit the proliferation and migration of OSCC cells,potentially through the mechanisms involving reduced glycolysis and cell cycle arrest in the G1 or G2 phase.