The effects of bufadienolides on HER2 overexpressing breast cancer cells
Abstract
HER2 is a proto-oncogene frequently amplified in human breast cancer, its overexpression is correlated with tamoxifen resistance and decreased recurrence-free survival. Arenobufagin and bufalin are homogeneous bufadienolides of cardiac glycosides agents. In this research, we studied the effects of arenobufagin and bufalin on cellular survival and proliferation of HER2 overexpressing breast cancer cells and the mechanism under the results including the direct effect on HER2 downstream pathways. Our results showed that arenobufagin and bufalin could significantly inhibit the proliferation and survival of HER2 overexpressing breast cancer cells, along with the declination of SRC-1, SRC-3, nuclear transcription factor E2F1, phosphorylated AKT, and ERK. And the combination of each bufadienolide in low dose with tamoxifen could significantly enhance the inhibitory effect of tamoxifen on HER2 overexpressing breast cancer cells. All above suggest that arenobufagin and bufalin may be potential therapy adjuvants for HER2 overexpressing breast cancer therapy.
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Bufalin has been shown to downregulate expression of transcriptional coactivators SRC-1 and SRC-3, as well as nuclear transcription factor E2F1.
“Furthermore, Bufalin has been shown to downregulate the expression of transcriptional coactivators SRC-1 and SRC-3, as well as the nuclear transcription factor E2F18,43.”
From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [43]
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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
- Authors
- Wang, T., Mu, L., Jin, H., Zhang, P., Wang, Y., Ma, X., Pan, J., Miao, J., & Yuan, Y.
- Affiliations
- Dalian Medical University (CN)
- Corresponding author
- Pan, Jinjin
- Miao, Jian
- Yuan, Yuhui
- ORCID
- Venue
- Tumor Biology
- Published
- 2015-12-12
- Volume
- 37
- Issue
- 6
- Pages
- 7155-7163
- ISSN
- 1010-4283 (ISSN-L)
- 1423-0380
- OpenAlex
- W2193036745
- Cited by
- 15
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2021: 2 · 2020: 3 · 2018: 1 · 2016: 2
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Tumor Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Liaoning Province
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Physical Sciences › Materials Science › Biomaterials › Phytochemistry and Bioactive Compounds
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
- Keywords
- bufadienolides, arenobufagin, bufalin, HER2 overexpression, breast cancer, tamoxifen resistance, combination therapy, cell proliferation, cell survival, Src family kinases, E2F1, Akt phosphorylation, ERK1/2 phosphorylation, cardiac glycosides, therapeutic adjuvant
- MeSH terms
- Proto-Oncogene Mas, Breast Neoplasms, Bufanolides, Cell Cycle, Female, Humans, Phosphorylation, Tumor Cells, Cultured, Blotting, Western, Signal Transduction, Gene Expression Regulation, Neoplastic, Apoptosis, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Cell Proliferation, Proto-Oncogene Proteins c-akt
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