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2000
Volume 28, Issue 5
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402
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Abstract

Background

Ovarian carcinoma is an aggressive gynecological malignancy. Kirenol, a diterpene compound, has recently gained attention for its potential anticancer properties. However, its exact anti-tumor mechanism remains largely unexplored.

Objective

In this study, we explored the inhibitory effects of Kirenol on ovarian cancer using network pharmacology and experiments and elucidated its underlying mechanisms.

Methods

Through the utilization of molecular docking, we established a network of protein-protein interactions (PPI), which unveiled CDK4 as an essential target. Additionally, gene enrichment and pathway analysis highlighted the significance of the PI3K/AKT pathway. The viability of ovarian cancer cells and normal ovarian epithelial cells was evaluated using CCK8 assays to determine the effect of Kirenol. Following tests, cell colony formation, wound healing, flow cytometry, and Western blotting were conducted to assess its impact on cell proliferation, metastasis, apoptosis, and the cell cycle.

Results

Kirenol significantly reduced the viability of ovarian cancer cells (SKOV3 and A2780) compared to normal ovarian epithelial cells (IOSE-80). Moreover, Kirenol efficiently suppressed the growth and movement, caused a cell cycle halt, and stimulated programmed cell death in SKOV3 and A2780 cells. Through molecular analysis, it was observed that Kirenol increased the expression of Bax while decreasing the expression of MMP2, MMP9, and Bcl-2. It also attenuated the phosphorylation of PI3K, AKT, and RB and downregulated CDK4 and CCND1 expression. Notably, co-treatment with the PI3K pathway inhibitor LY294002 enhanced the inhibitory effect of Kirenol on ovarian cancer cells.

Conclusion

In summary, the combined results of our network pharmacology analysis and tests emphasized that Kirenol hinders the growth of ovarian cancer cells, causes cell cycle arrest, enhances apoptosis, and hampers migration, possibly by regulating the PI3K/AKT/CDK4 signaling pathway.

© 2025 Bentham Science Publishers
© 2025 The Author(s). Published by Bentham Science Publisher. This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2024-02-26
2025-09-23

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Pharmacological Mechanisms of Kirenol against Ovarian Carcinoma: A Network Pharmacology and Experimental Validation Study In Vitro
Comb Chem High Throughput Screen 28, 825 (2025); https://doi.org/10.2174/0113862073289977240216075724
/content/journals/cchts/10.2174/0113862073289977240216075724
/content/journals/cchts/10.2174/0113862073289977240216075724
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  • Article Type:     Research Article
Keyword(s): apoptosis; cell cycle; Kiren; metastasis; ovarian carcinoma; PI3K/AKT/CDK4

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