Mistletoe Lectin Induces Apoptosis and Modulates the Cell Cycle in YD38 Oral Squamous Cell Carcinoma Cells

Abstract

Objectives: Despite progress in therapeutic interventions, squamous cell carcinoma of the oral cavity (OSCC) continues to pose a substantial burden on public health, with persistently poor patient outcomes. This investigation examines the growth-inhibitory and mechanistic effects of a plant-derived protein, Viscum album var. coloratum agglutinin (VCA), extracted from Korean mistletoe, against YD38 OSCC cells. Methods: The experimental protocols involved treating YD38 cells derived from human OSCC with escalating doses of VCA. Cell survival rates were quantified through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric analysis. Changes in apoptotic indices and cell cycle distribution were evaluated using flow cytometric techniques. Protein expression patterns associated with programmed cell death were determined via Western blot analysis. Statistical evaluation including effect size calculations, dose-response modeling, and correlation analyses were conducted to comprehensively evaluate VCA’s effects. Results: VCA exhibited dose-dependent cytotoxicity against YD38 cells. Flow cytometry analysis revealed significant increases in both early and late apoptotic populations at 100 and 1000 ng/mL VCA, with Cohen’s d values of 15.15 and 30.24, respectively, indicating large biological effects. Cell cycle analysis showed significant alterations in cell cycle distribution, and Western blot analysis demonstrated increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspase-3, indicating activation of the caspasedependent apoptotic pathway. Correlation analysis revealed strong relationships between different cellular responses (r > 0.95), suggesting coordinated cellular responses to VCA treatment. Conclusion: This study demonstrates that VCA exhibits potent anti-cancer effects against YD38 OSCC cells through apoptosis induction and cell cycle modulation, with quantitative analyses revealing strong effect sizes and coordinated cellular responses. These results add to our understanding of natural compounds in oncology and indicate that VCA could be a promising candidate in OSCC treatment development.