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

J Cell Biochem. 2024 Feb;125(2):e30504. doi: 10.1002/jcb.30504. Epub 2023 Nov 22.

Abstract

This 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.

Keywords: TEOA; autophagy; cisplatin; oral cancer; oral squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis
  • Autophagy
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm
  • Head and Neck Neoplasms*
  • Humans
  • Mouth Neoplasms* / drug therapy
  • Mouth Neoplasms* / pathology
  • Ursolic Acid

Substances

  • Cisplatin
  • Ursolic Acid
  • Antineoplastic Agents