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.
Biomolecules. 2020 Feb 5;10(2):245. doi: 10.3390/biom10020245.
Cancer stem cells are responsible for breast cancer initiation, metastasis, and relapse. Targeting breast cancer stem cells (BCSCs) using phytochemicals is a good strategy for the treatment of cancer. A silica gel, a reversed-phase C18 column (ODS), a Sephadex LH-20 gel, thin layer chromatography, and high-performance liquid chromatography (HPLC) were used for compound isolation from Saururus chinensis extracts. The isolated compound was identified as machilin D by mass spectrometry and nuclear magnetic resonance (NMR). Machilin D inhibited the growth and mammosphere formation of breast cancer cells and inhibited tumor growth in a xenograft mouse model. Machilin D reduced the proportions of CD44/CD24 and aldehyde dehydrogenase 1 (ALDH1)-positive cells. Furthermore, this compound reduced the nuclear localization of the NF-κB protein and decreased the IL-6 and IL-8 secretion in mammospheres. These results suggest that machilin D blocks IL-6 and IL-8 signaling and induces CSC death and thus may be a potential agent targeting BCSCs.
癌症干细胞是乳腺癌发生、转移和复发的根源。利用植物化学物质靶向乳腺癌干细胞（BCSCs）是治疗癌症的一种有效策略。本研究从白花蛇舌草提取物中采用硅胶、反相 C18 柱（ODS）、葡聚糖 LH-20 凝胶、薄层层析和高效液相色谱（HPLC）等方法进行化合物分离。通过质谱和核磁共振（NMR）鉴定分离得到的化合物为木兰脂素 D。木兰脂素 D 可抑制乳腺癌细胞的生长和球体形成，并抑制异种移植小鼠模型中的肿瘤生长。木兰脂素 D 降低了 CD44/CD24 和醛脱氢酶 1（ALDH1）阳性细胞的比例。此外，该化合物还降低了核定位的 NF-κB 蛋白，并减少了球体中 IL-6 和 IL-8 的分泌。这些结果表明，木兰脂素 D 阻断了 IL-6 和 IL-8 信号通路，并诱导 CSC 死亡，因此可能是一种针对 BCSCs 的潜在靶向药物。
