Bufalin Induces Programmed Necroptosis in Triple-Negative Breast Cancer Drug-Resistant Cell Lines through RIP1/ROS-Mediated Pathway
Abstract
Objective To explore the effect and mechanism of action of bufalin in triple-negative breast cancer (TNBC) drug-resistant cell lines. Methods The normal human mammary epithelial cell line, TNBC cell line, TNBC adriamycin-resistant cell line, and TNBC docetaxel-resistant cell line were treated with different doses of bufalin (0-1,000 nmol/L) at different time points (0-72 h). Propidium iodide staining, AV-FITC/PI double staining, Hoechst 33342/PI double staining and transmission electron microscopy (TEM) were used to evaluate the death patterns of the cell lines. Results Bufalin killed the TNBC cell line and its drug-resistant cell lines in a dose/time-dependent manner (all P Conclusions Bufalin could induce necroptosis through RIP1/ROS-mediated pathway to kill the drug-resistant TNBC cell lines. This finding provides critical experimental data and theoretical basis for the clinical application of bufalin to overcome the difficulties in the treatment of TNBC.
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Bufalin induced apoptosis, necroptosis, ferroptosis, autophagy, and senescence through AMPK, RIP1/ROS, DECR1, p62, and p53 pathways.
“Bufalin induced apoptosis, necroptosis, ferroptosis, autophagy, and senescence through AMPK, RIP1/ROS, DECR1, p62, and p53 pathways5,44–48.”
From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [47]
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Wu, S., Wu, X., Wang, Q., Chen, Z., Li, L., Chen, H., & Qi, H. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.156130 · Cited by 27 · see citing works
Jiang, S., Liu, K., Jiang, T., Li, H., Wei, X., Wan, X., Zhong, C., Gong, R., Chen, Z., Zou, C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62288-7 · Cited by 23 · see citing works
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- Authors
- Liu, X.-D., Song, C.-Y., Kong, C.-C., & Tian, X.
- Affiliations
- First Hospital of China Medical University (CN)
- Corresponding author
- Tian, Xin
- ORCID
- Tian, Xin
- Venue
- Chinese Journal of Integrative Medicine
- Published
- 2021-11-26
- Volume
- 28
- Issue
- 10
- Pages
- 900-908
- ISSN
- 1672-0415 (ISSN-L)
- 1993-0402
- OpenAlex
- W3215038008
- Cited by
- 21
- References
- 1
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 2
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chinese Journal of Integrative Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
- Keywords
- bufalin, triple-negative breast cancer, drug resistance, necroptosis, RIPK1, reactive oxygen species, doxorubicin resistance, docetaxel resistance, apoptosis, Nec-1, N-acetylcysteine, tumor necrosis factor receptor 1, caspase-3
- MeSH terms
- Docetaxel, Necroptosis, Antioxidants, Bufanolides, Cell Line, Cysteine, Doxorubicin, Humans, Propidium, Tumor Necrosis Factor-alpha, Fluorescein-5-isothiocyanate, Apoptosis, Reactive Oxygen Species, Receptors, Tumor Necrosis Factor, Cell Line, Tumor, Caspase 3, Triple Negative Breast Neoplasms
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