Citrus polymethoxyflavones degrade estrogen receptor-alpha (ERα) and combine with tamoxifen for the treatment of estrogen receptor-positive breast cancer.

柑橘多甲氧基黄酮降解雌激素受体 α （ ER α ） 并与他莫昔芬联合治疗雌激素受体阳性乳腺癌。

• 影响指数: 3.776
• 发表时间: 2024 Jun 30
• 来源期刊: Heliyon
• DOI: 10.1016/j.heliyon.2024.e33104
• PMID: 39022050
• 文章类型: Journal Article
• 作者列表: Wang Y,Sun M,He Z,Han Y,Song Y,Liang J,Wang H,Qin Y,Deng Z

关键词: Citrus; Estrogen receptor; Polymethoxyflavones; Tamoxifen; Ubiquitination

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.

摘要

雌激素受体阳性(ER+)乳腺癌严重危害全球女性身心健康,ER靶向治疗至关重要。这里,我们发现柑橘富含多甲氧基黄酮（PMFs）的水解物（C-H）及其主要成分（金黄素和3-甲氧基金黄素）通过泛素-蛋白酶体途径有效降解ERα蛋白，从而损害ER+乳腺癌细胞的增殖。此外，我们的研究表明，C-H联合他莫昔芬（TAM）在体外抑制ER乳腺癌的细胞增殖。进一步证实,C-H降低了荷瘤129小鼠体内ER+乳腺癌的肿瘤生长,并提高了他莫昔芬的功效。我们的研究表明，柑橘PMFs通过靶向ERα蛋白降解在乳腺癌治疗中具有潜在的药物和保健产品应用。