Scutellarein Induces Apoptosis in SCC-25 Oral Squamous Cell Carcinoma Cells Through Suppression of the PI3K/Akt Pathway

Background/Aim: Oral squamous cell carcinoma (OSCC) remains a major global health burden with poor long-term survival, highlighting the need for novel therapeutic agents. This study aimed to evaluate the anticancer potential of scutellarein and to elucidate its underlying mechanisms in OSCC cells.

Materials and Methods: The OSCC cell line SCC-25 and normal oral fibroblasts (OFs) were used in this study. Morphological assessment, MTT, ELISA, JC-1 staining, and immunoblotting assays were performed to evaluate membrane blebbing, cell viability, cytokeratin-18 fragment release, changes in mitochondrial membrane potential (MMP), and protein expression, respectively. In addition, PI3Kinase catalytic subunit alpha (PIK3CA) overexpression was used to examine the involvement of the PI3K/Akt pathway in the effects mediated by scutellarein.

Results: Scutellarein preferentially reduced SCC-25 cell viability, with IC₅₀ values of 25.6 μM in SCC-25 cells and 206.6 μM in OFs, indicating tumor-selective cytotoxicity. Scutellarein induced apoptosis in SCC-25 cells, as evidenced by increased membrane blebbing, elevated levels of cleaved poly(ADP-ribose) polymerase, and enhanced release of cytokeratin-18 fragments. Mechanistically, scutellarein upregulated Fas, disrupted MMP, and increased the levels of cleaved caspase-8, caspase-9, and caspase-3. Scutellarein also suppressed phosphoinositide 3-kinase (PI3K)/Akt phosphorylation. Importantly, PIK3CA overexpression increased Akt phosphorylation and attenuated scutellarein-induced cytokeratin-18 fragment release and caspase cascade activation, further supporting the involvement of PI3K/Akt inhibition in the anticancer effects of scutellarein.

Conclusion: Scutellarein exerts tumor-selective cytotoxic and pro-apoptotic effects in SCC-25 cells, at least in part, by suppressing the PI3K/Akt pathway.