Ko Yu-Chan, Liu Ren, Sun Hu-Nan, Yun Bong-Sik, Choi Hack Sun, Lee Dong-Sun
Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju 63243, Korea.
Stem Cell Therapy and Regenerative Biology Laboratory, College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing 163319, China.
Pharmaceuticals (Basel). 2022 May 26;15(6):664. doi: 10.3390/ph15060664.
Breast cancer is the leading cause of global cancer incidence and breast cancer stem cells (BCSCs) have been identified as the target to overcome breast cancer in patients. In this study, we purified a BCSC inhibitor from H.Lév. leaves through several open column and high-performance liquid chromatography via activity-based purification. The purified cancer stem cell (CSC) inhibitor was identified as dihydroconiferyl ferulate using nuclear magnetic resonance and mass spectrometry. Dihydroconiferyl ferulate inhibited the proliferation and mammosphere formation of breast cancer cells and reduced the population of CD44/CD24 cells. Dihydroconiferyl ferulate also induced apoptosis, inhibited the growth of mammospheres and reduced the level of total and nuclear EGFR protein. It suppressed the EGFR levels, the interaction of Stat3 with EGFR, and c-Myc protein levels. Our findings show that dihydroconiferyl ferulate reduced the level of nuclear epidermal growth factor receptor (EGFR) and induced apoptosis of BCSCs through nEGFR/Stat3-dependent c-Myc deregulation. Dihydroconiferyl ferulate exhibits potential as an anti-CSC agent through nEGFR/Stat3/c-Myc signaling.
乳腺癌是全球癌症发病的主要原因，乳腺癌干细胞（BCSCs）已被确定为攻克乳腺癌患者的靶点。在本研究中，我们通过基于活性的纯化方法，利用多个开放柱和高效液相色谱从H.Lév.叶中纯化出一种BCSC抑制剂。使用核磁共振和质谱法将纯化的癌症干细胞（CSC）抑制剂鉴定为二氢松柏基阿魏酸酯。二氢松柏基阿魏酸酯抑制乳腺癌细胞的增殖和乳腺球形成，并减少CD44/CD24细胞群体。二氢松柏基阿魏酸酯还诱导细胞凋亡，抑制乳腺球生长，并降低总EGFR蛋白和核EGFR蛋白水平。它抑制EGFR水平、Stat3与EGFR的相互作用以及c-Myc蛋白水平。我们的研究结果表明，二氢松柏基阿魏酸酯通过nEGFR/Stat3依赖的c-Myc失调降低核表皮生长因子受体（EGFR）水平并诱导BCSCs凋亡。二氢松柏基阿魏酸酯通过nEGFR/Stat3/c-Myc信号传导展现出作为抗CSC药物的潜力。
