Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Korea.
Subtropical/tropical organism gene bank, Jeju National University, Jeju 63243, Korea.
Molecules. 2020 Jun 3;25(11):2599. doi: 10.3390/molecules25112599.
Breast cancer stem cells (BCSCs) are responsible for tumor chemoresistance and recurrence. Targeting CSCs using natural compounds is a novel approach for cancer therapy. A CSC-inhibiting compound was purified from citrus extracts using silica gel, gel filtration and high-pressure liquid chromatography. The purified compound was identified as tangeretin by using nuclear magnetic resonance (NMR). Tangeretin inhibited cell proliferation, CSC formation and tumor growth, and modestly induced apoptosis in CSCs. The frequency of a subpopulation with a CSC phenotype (CD44/CD24) was reduced by tangeretin. Tangeretin reduced the total level and phosphorylated nuclear level of signal transducer and activator of transcription 3 (Stat3). Our results in this study show that tangeretin inhibits the Stat3 signaling pathway and induces CSC death, indicating that tangeretin may be a potential natural compound that targets breast cancer cells and CSCs.
乳腺癌干细胞（BCSCs）是肿瘤化疗耐药和复发的根源。使用天然化合物靶向 CSCs 是癌症治疗的新方法。使用硅胶、凝胶过滤和高压液相色谱从柑橘提取物中纯化出一种具有抑制 CSCs 活性的化合物。通过核磁共振（NMR）鉴定该纯化化合物为橘红素。橘红素抑制细胞增殖、CSC 形成和肿瘤生长，并适度诱导 CSCs 凋亡。具有 CSC 表型（CD44/CD24）的亚群频率因橘红素而降低。橘红素降低了信号转导和转录激活因子 3（Stat3）的总水平和磷酸化核水平。我们在这项研究中的结果表明，橘红素抑制 Stat3 信号通路并诱导 CSC 死亡，表明橘红素可能是一种潜在的天然化合物，可作为针对乳腺癌细胞和 CSCs 的靶标。
