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Triptonide induces apoptosis and inhibits the proliferation of ovarian cancer cells by activating the p38/p53 pathway and autophagy.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2024 Aug 01; Vol. 110, pp. 117788. Date of Electronic Publication: 2024 Jun 06. - Publication Year :
- 2024
-
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.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Subjects :
- Humans
Female
Structure-Activity Relationship
Drug Screening Assays, Antitumor
Dose-Response Relationship, Drug
Cell Line, Tumor
Molecular Structure
Antineoplastic Agents pharmacology
Antineoplastic Agents chemistry
Antineoplastic Agents chemical synthesis
Antineoplastic Agents, Phytogenic pharmacology
Antineoplastic Agents, Phytogenic chemistry
Apoptosis drug effects
Autophagy drug effects
Cell Proliferation drug effects
Ovarian Neoplasms drug therapy
Ovarian Neoplasms pathology
Ovarian Neoplasms metabolism
Tumor Suppressor Protein p53 metabolism
p38 Mitogen-Activated Protein Kinases metabolism
Triterpenes pharmacology
Triterpenes chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 110
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38964974
- Full Text :
- https://doi.org/10.1016/j.bmc.2024.117788