Triptonide induces apoptosis and inhibits the proliferation of ovarian cancer cells by activating the p38/p53 pathway and autophagy

Bioorg Med Chem. 2024 Aug 1:110:117788. doi: 10.1016/j.bmc.2024.117788. Epub 2024 Jun 6.

Abstract

Ovarian cancer is a common malignant tumor in women, and 70 % of ovarian cancer patients are diagnosed at an advanced stage. Drug chemotherapy is an important method for treating ovarian cancer, but recurrence and chemotherapy resistance often lead to treatment failure. In this study, we screened 10 extracts of Tripterygium wilfordii, a traditional Chinese herb, and found that triptonide had potent anti-ovarian cancer activity and an IC50 of only 3.803 nM against A2780 cell lines. In addition, we determined that triptonide had a better antitumor effect on A2780 cell lines than platinum chemotherapeutic agents in vitro and that triptonide had no significant side effects in vivo. We found that triptonide induced apoptosis in ovarian cancer cells through activation of the p38/p53 pathway and it also induced cell cycle arrest at the S phase. In addition, we demonstrated that triptonide could activate lethal autophagy, which led to growth inhibition and cell death in ovarian cancer cells, resulting in an anti-ovarian cancer effect. Triptonide exerts its anti-ovarian cancer effect through activation of the p38/p53 pathway and induction of autophagy to promote apoptosis, which provides a new candidate drug and strategy for the treatment of ovarian cancer.

Keywords: Antitumor; Apoptosis; Autophagy; Ovarian cancer; Triptonide.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis* / drug effects
  • Autophagy* / drug effects
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Molecular Structure
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Structure-Activity Relationship
  • Triterpenes* / chemistry
  • Triterpenes* / pharmacology
  • Tumor Suppressor Protein p53* / metabolism
  • p38 Mitogen-Activated Protein Kinases* / metabolism

Substances

  • triptonide
  • Tumor Suppressor Protein p53
  • p38 Mitogen-Activated Protein Kinases
  • Triterpenes
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic