三阴性乳腺癌 (TNBC) 占所有乳腺癌的 15%，且具有高度侵袭性。尽管最初对化疗有积极反应，但大多数患者会经历疾病快速进展，导致复发和转移。这是由于肿瘤内存在乳腺癌干细胞（BCSC），其特点是自我更新、多能性和耐药机制。由于缺乏特定靶标，传统疗法无法根除 BCSC，因此针对 BCSC 变得至关重要。姜黄素是一种从姜黄 (Curcuma longa) 中提取的多酚，对乳腺癌细胞和 BCSC 具有抗癌作用。人们建议使用姜黄素衍生物作为克服姜黄素在人体中的生物利用度和溶解度问题的方法，从而增强其抗癌作用。本研究的目的是评估源自天然多酚表没食子儿茶素没食子酸酯 (EGCG)（TL1、TL2）和姜黄素衍生物（TL3、TL4、TL5 和 TL6）的六种合成化合物对 TNBC 间充质干细胞和分子的影响样细胞系。还通过乳腺球抑制测定并通过蛋白质印迹研究不同的 BCSC 标记来测定化合物针对 BCSC 的活性。最后，对最有希望的化合物进行了药物组合测定，以评估它们与化疗药物阿霉素、顺铂和紫杉醇的潜在协同作用。结果表明，化合物对 TNBC 细胞系和 BCSC 表现出特异性细胞毒性。有趣的是，姜黄素衍生物 TL3 与阿霉素和顺铂的组合在 TNBC 细胞中显示出协同作用。

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is highly aggressive. Despite an initial positive response to chemotherapy, most patients experience rapid disease progression leading to relapse and metastasis. This is attributed to the presence of breast cancer stem cells (BCSCs) within the tumor, which are characterized by self-renewal, pluripotency, and resistance mechanisms. Targeting BCSCs has become critical as conventional therapies fail to eradicate them due to a lack of specific targets. Curcumin, a polyphenol derived from turmeric (Curcuma longa), exhibits anticancer effects against breast cancer cells and BCSCs. The use of curcumin derivatives has been suggested as an approach to overcome the bioavailability and solubility problems of curcumin in humans, thereby increasing its anticancer effects. The aim of this study was to evaluate the cellular and molecular effects of six synthetic compounds derived from the natural polyphenol epigallocatechin gallate (EGCG) (TL1, TL2) and curcumin derivatives (TL3, TL4, TL5, and TL6) on a TNBC mesenchymal stem-like cell line. The activity of the compounds against BCSCs was also determined by a mammosphere inhibition assay and studying different BCSC markers by Western blotting. Finally, a drug combination assay was performed with the most promising compounds to evaluate their potential synergistic effects with the chemotherapeutic agents doxorubicin, cisplatin, and paclitaxel. The results showed that compounds exhibited specific cytotoxicity against the TNBC cell line and BCSCs. Interestingly, the combination of the curcumin derivative TL3 with doxorubicin and cisplatin displayed a synergistic effect in TNBC cells.