Abstract：
Breast cancer is the leading cause of cancer deaths in women worldwide. EF-24, an analog of curcumin, has been shown to possess promising anticancer effects. However, the underlying mechanism remains elusive. In the present study, the inhibitory effect of EF-24 against one breast cancer cell line, MDA-MB-231, and its anti-migration ability were assessed by MTT, wound healing, and Transwell assay. Furthermore, we found that EF-24 could induce initiation of autophagy as evidenced by fluorescence and electron microscope observation. EF-24 also induced mitochondrial apoptosis in MDA-MB-231 cells as detected by Hoechst 33342 staining, flow cytometry analysis, and western blot analysis. In addition, the early autophagy inhibitor 3-MA could reduce the cleavage of PARP protein and protect cells from EF-24-induced apoptosis, while the autophagy inducer (rapamycin) could enhance the anticancer effect of EF-24 in MDA-MB-231 cells, which suggest that EF-24 induces crosstalk between autophagy and apoptosis, which herein participate in the antiproliferative effect of EF-24 in breast cancer cells. Moreover, removal of EF-24-activated ROS with NAC significantly reversed migration ability of MDA-MB-231 cells, indicating that EF-24 exerted an inhibitory effect through a ROS-mediating pathway. These results will help to elucidate the antitumor mechanism of curcumin analogs and to explore future potential clinical applications.
摘要：
乳腺癌是全球女性癌症死亡的主要原因。EF-24，姜黄素的类似物，已被证明具有有希望的抗癌作用。然而,潜在的机制仍然难以捉摸。在本研究中,EF-24对一种乳腺癌细胞系的抑制作用，MDA-MB-231，并通过MTT评估其抗迁移能力，伤口愈合，和Transwell分析。此外，我们发现EF-24可以诱导自噬的启动，荧光和电子显微镜观察证明。EF-24还诱导MDA-MB-231细胞的线粒体凋亡，如通过Hoechst33342染色检测，流式细胞术分析,和蛋白质印迹分析。此外,早期自噬抑制剂3-MA可以减少PARP蛋白的裂解，保护细胞免受EF-24诱导的凋亡，自噬诱导剂(雷帕霉素)可增强EF-24对MDA-MB-231细胞的抗癌作用,这表明EF-24诱导自噬和凋亡之间的串扰，其在本文中参与EF-24在乳腺癌细胞中的抗增殖作用。此外，用NAC去除EF-24激活的ROS显著逆转MDA-MB-231细胞的迁移能力,表明EF-24通过ROS介导途径发挥抑制作用。这些结果将有助于阐明姜黄素类似物的抗肿瘤机制并探索未来的潜在临床应用。
