Guan Qi-Xin, Yu Long-Bo, Wang Peng, Hu Qing-Yuan, Tan Cai-Ping
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, Guangzhou 510006, P. R. China.
ACS Pharmacol Transl Sci. 2025 May 29;8(6):1804-1813. doi: 10.1021/acsptsci.5c00219. eCollection 2025 Jun 13.
Triple-negative breast cancer (TNBC) is an aggressive malignancy, with limited targeted treatment options. In this study, we developed a novel triphenylphosphine (TPP)-modified deferasirox (DFX) titanium complex () to disrupt iron homeostasis in TNBC cells through transmetalation. depletes the labile iron pool, triggering a compensatory upregulation of transferrin receptor 1 (TfR1) in response to an intracellular iron deficiency. The disruption of iron metabolism by increases reactive oxygen species (ROS) levels, which in turn lead to mitochondrial dysfunction and DNA damage, ultimately inhibiting cancer cell growth. In vivo studies further demonstrated that inhibits tumor growth without significant toxicity to major organs. These findings suggest that is a promising therapeutic candidate for TNBC, as it exploits the disruption of iron metabolism and ROS pathways to enhance its anticancer efficacy.
三阴性乳腺癌（TNBC）是一种侵袭性恶性肿瘤，靶向治疗选择有限。在本研究中，我们开发了一种新型的三苯基膦（TPP）修饰的地拉罗司（DFX）钛配合物（），通过金属转移作用破坏TNBC细胞中的铁稳态。 耗尽不稳定铁池，响应细胞内铁缺乏触发转铁蛋白受体1（TfR1）的代偿性上调。 通过 破坏铁代谢会增加活性氧（ROS）水平，进而导致线粒体功能障碍和DNA损伤，最终抑制癌细胞生长。体内研究进一步表明， 可抑制肿瘤生长，而对主要器官无明显毒性。这些发现表明， 是TNBC很有前景的治疗候选物，因为它利用铁代谢和ROS途径的破坏来增强其抗癌功效。
