College of Pharmaceutical Sciences, Guizhou University of Traditional Chinese Medicine, 4, Dongqing Road, Huaxi District, Guiyang 550025, China.
Department of Medicinal Chemistry, College of Pharmaceutical Sciences of Capital Medical University, 10, Xitoutiao, Right Anmen West, Fengtai District, Beijing 100069, China.
Biomed Pharmacother. 2024 Sep;178:117158. doi: 10.1016/j.biopha.2024.117158. Epub 2024 Jul 22.
Triple-negative breast cancer (TNBC) still one of the most challenging sub-type in breast cancer clinical. Caffeic acid (CA) derived from effective components of traditional Chinese herbal medicine has been show potential against TNBCs. Our research has found that CA can inhibit the proliferation of TNBC cells while also suppressing the size of cancer stem cell spheres. Additionally, it reduces reactive oxygen species (ROS) levels and disruption of mitochondrial membrane potential. Simultaneously, CA influences the stemness of TNBC cells by reducing the expression of the stem cell marker protein CD44. Furthermore, we have observed that CA can modulate the FOXO1/FIS signaling pathway, disrupting mitochondrial function, inducing mitochondrial autophagy, and exerting anti-tumor activity. Additionally, changes in the immune microenvironment were detected using a mass cytometer, we found that CA can induce M1 polarization of macrophages, enhancing anti-tumor immune responses to exert anti-tumor activity. In summary, CA can be considered as a lead compound for further research in targeting TNBC.
三阴性乳腺癌（TNBC）仍然是乳腺癌临床中最具挑战性的亚型之一。咖啡酸（CA）来源于中草药的有效成分，已被证明对 TNBC 具有潜在的作用。我们的研究发现，CA 可以抑制 TNBC 细胞的增殖，同时抑制肿瘤干细胞球体的大小。此外，它还降低了活性氧（ROS）水平并破坏了线粒体膜电位。同时，CA 通过降低干细胞标志物蛋白 CD44 的表达来影响 TNBC 细胞的干性。此外，我们观察到 CA 可以调节 FOXO1/FIS 信号通路，破坏线粒体功能，诱导线粒体自噬，并发挥抗肿瘤活性。此外，使用质谱细胞仪检测到免疫微环境的变化，我们发现 CA 可以诱导巨噬细胞的 M1 极化，增强抗肿瘤免疫反应，发挥抗肿瘤活性。总之，CA 可以被认为是针对 TNBC 的进一步研究的先导化合物。
