Diterpenoid from Croton tonkinensis as a Potential Radiation Sensitizer in Oral Squamous Cell Carcinoma: An In Vitro Study

Radiotherapy combined with a radiosensitizer represents an important treatment for head and neck squamous cell carcinoma (HNSCC). Only a few chemotherapy agents are currently approved as radiosensitizers for targeted therapy. Oral squamous cell carcinoma is one of the deadliest cancers, with approximately ~500,000 new diagnosed cases and 145,000 deaths worldwide per year. The incidence of new cases continues to increase in developing countries. This study aimed to investigate the effect of <i>Croton tonkinensis</i> and <i>Curcuma longa</i> on cell viability in OSCC cells. The HNSCC cell line OML1 and its radiation-resistant clone OML1-R were used. The anticancer effect and the mechanism of action of <i>Croton tonkinensis</i> and <i>Curcuma longa</i> in OSCC cells were analyzed by using cell viability assays, Western blot analysis, and Tranwell migration assays. The results showed that <i>Croton tonkinensis</i> concentration-dependently reduced the viability of OML1 and OML1-R (radioresistant) cells by downregulating the levels of AKT/mTOR mediators, such as p110α, p85, pAKT (ser473), p-mTOR (ser2448), and p-S6 Ribosomal (ser235/236). We found that cotreatment of OML1 and OML1R cells with either zVAD-FMK (apoptosis inhibitor), Ferrostatin-1 (Fer-1, a ferroptosis inhibitor), or chloroquine (CQ, an autophagy inhibitor) markedly reduced cell death. These results demonstrate that <i>Croton tonkinensis</i> exhibits anti-proliferation activity and highlight the therapeutic potential of small-molecule inhibitors against PI3K/mTOR signaling for radiosensitization in HNC treatment.