Wang Yiyu, Sun Meng, He Zhong, Han Ying, Song Yinhong, Liang Jianjia, Wang Huimin, Qin Ye, Deng Zhangshuang
Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002, China.
Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang 443002, China.
Heliyon. 2024 Jun 14;10(12):e33104. doi: 10.1016/j.heliyon.2024.e33104. eCollection 2024 Jun 30.
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 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 . It was further confirmed that C-H decreased tumor growth of ER breast cancer in tumor-bearing 129 mice in 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.
雌激素受体阳性（ER）乳腺癌严重危害全球女性身心健康，靶向ER的治疗至关重要。在此，我们发现富含柑橘多甲氧基黄酮（PMFs）的水解产物（C-H）及其主要成分（川陈皮素和3-甲氧基川陈皮素）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与他莫昔芬（TAM）联合使用可抑制ER乳腺癌细胞在体内的增殖。进一步证实，C-H可降低荷瘤129小鼠体内ER乳腺癌的肿瘤生长，并提高他莫昔芬的疗效。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作为药物和保健品的潜在应用价值。
