Bufalin inhibits ovarian carcinoma via targeting mTOR/HIF‐α pathway
Abstract
Ovarian cancer is a severe health threat for women with increased incidence and stymied development in diagnosis and therapy. Drug resistance is still a big challenge. Bufalin is a multi‐functional steroid‐like compound extracted from natural product Chansu and has been tested as antitumour agent recently. The application and mechanism of bufalin in ovarian cancer remain unclear yet. Bufalin was first examined in ovarian epithelial cancer cell as well as primary ovarian tissue to evaluate its inhibitory activity in cell growth and migration, followed by the validation in xenograft tumour model and the patient samples. Bufalin is well tolerated by normal ovarian tissue at up to 40 μM and suppresses the cell growth and migration at 10 μM and xenograft tumour growth at 0.1mg/kg dosage. Bufalin inhibits the mammalian target of rapamycin (mTOR) activation and subsequently decreases hypoxia‐induced factor 1 alpha (HIF‐1α) level. Overexpression of HIF‐1α could abolish the pro‐apoptotic and antimigration activity of bufalin in cell culture. Strikingly, low HIF‐1α level was correlated with improved responsiveness to cisplatin treatment in ovarian cancer patients. Bufalin was a potent inhibitor of cell growth and migration in ovarian cancer cells through suppression of mTOR activation and HIF‐1α induction. Bufalin could be used to enhance the efficacy of cisplatin in ovarian cancer patients.
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Bufalin has been previously reported to associate with mTOR and AR.
“Given that the association of Bufalin with mTOR and AR has been previously reported26,27, we evaluated the binding of Bufalin to recombinant human ESR1, PRKCD, and CYP17A1 proteins using surface plasmon resonance (SPR) assays.”
From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [26]
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- Authors
- Su, S., Dou, H., Wang, Z., & Zhang, Q.
- Affiliations
- Central Hospital of Zibo (CN)
- Department of Gynecology Zibo Central Hospital Shandong China
- Department of Obstetrical Zibo Maternal and Child Health Hospital Shandong China
- Corresponding author
- Zhang, Qinghua
- Venue
- Basic & Clinical Pharmacology & Toxicology
- Publisher
- Wiley
- Published
- 2020-10-02
- Volume
- 128
- Issue
- 2
- Pages
- 224-233
- ISSN
- 1742-7835 (ISSN-L)
- 1742-7843
- OpenAlex
- W3086048373
- Cited by
- 32
- References
- 31
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 1
- FWCI
- 4.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Basic & Clinical Pharmacology & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- bufalin, ovarian cancer, mTOR, HIF-1α, Chansu, cisplatin resistance, cell migration, apoptosis, tumor xenografts, drug resistance
- MeSH terms
- Carcinoma, Ovarian Epithelial, Animals, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Bufanolides, Cell Movement, Cisplatin, Female, Humans, Mice, Nude, Neoplasm Invasiveness, Ovarian Neoplasms, Tumor Cells, Cultured, Signal Transduction, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Xenograft Model Antitumor Assays, Cell Line, Tumor, Tumor Burden, Cell Proliferation, Mice, Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine Kinases
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