Differential Effects of Curcumin and Cordycepin on Oral Squamous Cell Carcinoma Cells: ROS-Mediated Cytotoxicity and Real-Time Morphological Analysis

Oral squamous cell carcinoma (OSCC) remains a major clinical challenge, highlighting the need for novel therapeutic strategies. Natural bioactive compounds such as curcumin (Cu) and cordycepin (Co) have shown anticancer potential; however, their effects on cancer cell morphology and behavior remain incompletely characterized. This study assessed the individual and combined effects of Cu and Co on oral squamous cell carcinoma cells (OECM-1) and normal human gingival epithelial cells (HGEpiC) over 24 and 48 h. Metabolic activity, membrane integrity, oxidative stress, apoptosis, and inflammatory responses were evaluated using MTT, LDH, ROS-H2O2, caspase 3/7, and NO assays. Label-free digital holographic microscopy enabled real-time monitoring of morphology, motility, and proliferation. Both compounds induced ROS-mediated cytotoxicity, but responses were notably more pronounced in OECM-1 than in HGEpiC cells. Real-time morphological profiling revealed distinct response patterns: Co primarily exerted cytostatic effects, whereas Cu induced cell shrinkage, impaired motility, and inhibited cell division. The combination treatment (CC) largely reflected Cu-driven morphological and functional changes, with Co coexisting without counteracting Cu’s effects. Taken together, these findings reveal compound-specific mechanisms of action for Cu and Co in OSCC therapy.