Bufalin induces ferroptosis by modulating the 2,4-dienoyl-CoA reductase (DECR1)-SLC7A11 axis in breast cancer
Abstract
Breast cancer (BC) is a leading cause of cancer-related mortality worldwide. 2,4-dienoyl-CoA reductase (DECR1), an auxiliary component of beta-oxidation, has been recognized for its role in enhancing lipid peroxidation and inducing ferroptosis in prostate cancer. However, its involvement in breast cancer remains largely unexplored. Our study revealed a notably elevated expression of DECR1 in breast cancer tissues, which correlated with increased malignant characteristics. Importantly, the overexpression of DECR1 significantly enhanced proliferation and migration capabilities in MDA-MB-231 cells. Through a comprehensive high-content screening approach, we identified bufalin and its derivative as potent inhibitors of DECR1 expression. Notably, bufalin demonstrated the highest binding energy during molecular docking studies and was found to promote the degradation of DECR1 via autophagy and ubiquitination. Furthermore, bufalin induced ferroptosis in MDA-MB-231 cells by modulating levels of malondialdehyde (MDA), triglycerides (TG), reactive oxygen species (ROS) and Fe 2+ while downregulating the expression of hormone-sensitive lipase (HSL), ferritin heavy chain protein 1 (FPN), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4). These effects were counteracted by DECR1 overexpression. In vivo experiments demonstrated that bufalin inhibited the tumor growth, while decreasing the expression levels of HSL, FPN, SLC7A11, and GPX4, alongside increasing l…
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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 [44]
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- Authors
- Wu, S., Wu, X., Wang, Q., Chen, Z., Li, L., Chen, H., & Qi, H.
- Affiliations
- Southwest University (CN)
- Chongqing University (CN)
- Corresponding author
- Chen, Zhigang
- Chen, Hongdan
- Qi, Hongyi
- Venue
- Phytomedicine
- Publisher
- Elsevier BV
- Published
- 2024-12
- Volume
- 135
- Pages
- 156130
- ISSN
- 0944-7113 (ISSN-L)
- OpenAlex
- W4403117562
- Cited by
- 27
- References
- 45
- Citations by year
- 2026: 12 · 2025: 15
- FWCI
- 7.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Phytomedicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Chongqing Municipality (CSTB2023NSCQ-MSX0870)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Physical Sciences › Chemistry › Organic Chemistry › Ferrocene Chemistry and Applications
- Keywords
- bufalin, ferroptosis, DECR1, SLC7A11, GPX4, breast cancer, lipid peroxidation, fatty acid beta-oxidation, autophagy, ubiquitination, MDA-MB-231 cells, tumor growth inhibition, 4-hydroxynonenal, malondialdehyde, reactive oxygen species, iron accumulation, targeted therapy
- MeSH terms
- Ferroptosis, Phospholipid Hydroperoxide Glutathione Peroxidase, Animals, Breast Neoplasms, Bufanolides, Cell Movement, Female, Humans, Malondialdehyde, Mice, Inbred BALB C, Mice, Nude, Reactive Oxygen Species, Amino Acid Transport System y+, Cell Line, Tumor, Cell Proliferation, Mice, Molecular Docking Simulation
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