Taiwanoid A Inhibits Oral Squamous Cell Carcinoma (OSCC) Progression Through EGFR-Associated Signaling

Oral squamous cell carcinoma (OSCC) remains a significant global health challenge with limited effective therapeutic options. In this study, diterpenoids were isolated from Taiwania cryptomerioides and evaluated for their anticancer activities against OSCC. Ten diterpenoids were identified by MPLC, HPLC, and NMR analyses, among which taiwanoid A exhibited the strongest inhibitory effect on CAL27 cells. Functional assays demonstrated that taiwanoid A significantly suppressed cell proliferation, migration, invasion, tumor cell tube formation and colony formation while promoting apoptosis in a dose-dependent manner. Transcriptome analysis and Western blotting revealed that taiwanoid A modulated Wnt/β-catenin-associated, MAPK, and PI3K-AKT signaling. Target prediction, molecular docking, and cellular thermal shift assays identified EGFR as a potential target of taiwanoid A. Furthermore, EGFR knockdown attenuated the inhibitory effects of taiwanoid A on downstream signaling and malignant cellular behaviors, indicating that its anticancer activity is partially dependent on EGFR-associated signaling inhibition. In vivo xenograft experiments further confirmed that taiwanoid A effectively suppressed CAL27 tumor growth. Collectively, these findings support significant anti-OSCC activity of taiwanoid A and implicate EGFR-associated signaling pathways in this activity, highlighting its potential as a promising therapeutic candidate for oral cancer.