2α, 3α, 24‐Thrihydroxyurs‐12‐en‐24‐ursolic acid enhances the cytotoxic effect of cisplatin on oral cancer cells by down‐regulating autophagy

Abstract

AbstractThis study aimed to investigate the effect and mechanism of 2α, 3α, 24‐thrihydroxyurs‐12‐en‐24‐ursolic acid (TEOA) alone or in combination with cisplatin on oral cancer. TEOA, a pentacyclic triterpenoid compound isolated from the roots of Actinidia eriantha, has demonstrated antitumor activity in preclinical experiments. However, its role in oral cancer remains poorly understood. Our findings revealed that a low concentration of TEOA did not exhibit significant cytotoxicity against oral squamous cell carcinoma cells. However, when combined with cisplatin, TEOA showed a significant therapeutic effect. The combined treatments resulted in a significant inhibition of proliferation and migration and a significant increase in apoptosis of squamous cell carcinoma cells. Cisplatin exposure increased autophagy levels, which may contribute to chemoresistance. Of note, the presence of TEOA significantly inhibited cisplatin‐induced autophagy, leading to improved chemotherapy efficacy. Our findings indicate that a mild low dosage of TEOA may enhance the cytotoxic effect of cisplatin by downregulating autophagy in oral cancer cells.