Citrus polymethoxyflavones degrade estrogen receptor-alpha (ERα) and combine with tamoxifen for the treatment of estrogen receptor-positive breast cancer
- PMID: 39022050
- PMCID: PMC11252954
- DOI: 10.1016/j.heliyon.2024.e33104
Citrus polymethoxyflavones degrade estrogen receptor-alpha (ERα) and combine with tamoxifen for the treatment of estrogen receptor-positive breast cancer
Abstract
Estrogen receptor-positive (ER+) breast cancer seriously endangers the women's physical and mental health worldwide and ER targeting therapy is vital. Here, we found that a citrus polymethoxyflavones (PMFs)-rich hydrolysate (C-H) and its major components (nobiletin and 3-methoxynobiletin) potently degrade ERα protein via the ubiquitin-proteasome pathway, thereby impairing the proliferation of ER+ breast cancer cells. Moreover, our study exhibited that C-H combined with tamoxifen (TAM) inhibited the cell proliferation of ER+ breast cancer in vitro. It was further confirmed that C-H decreased tumor growth of ER+ breast cancer in tumor-bearing 129 mice in vivo and improved the efficacy of tamoxifen. Our study revealed that the citrus PMFs have potential applications as pharmaceutical and healthcare products in breast cancer treatment by targeting ERα protein degradation.
Keywords: Citrus; Estrogen receptor; Polymethoxyflavones; Tamoxifen; Ubiquitination.
© 2024 The Authors. Published by Elsevier Ltd.
Conflict of interest statement
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Zhangshuang Deng reports financial support was provided by 10.13039/501100001809National Natural Science Foundation of China. Jianjia Liang reports financial support was provided by Yichang Applied Basic Research Project. Ye Qin reports financial support was provided by opening foundation of Tumor Microenvironment and Immunotherapy Key Laboratory of Hubei province in China. Zhangshuang deng has patent pending to China Three Gorges University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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