Gou, Yi, Chen, MeiRong, Li, Shanhe, Deng, JunGang, Li, Jinlong, Fang, GuiHua, Yang, Feng, and Huang, GuoJin
Anticancer agents that present nonapoptotic cell death pathways are required for treating apoptosis-resistant pancreatic cancer. Here, we synthesized three fluorescent dithiocarbazate–copper complexes, {[CuII(L)(Cl)] 1, [CuII2(L)2(NO3)2] 2, and [CuII2CuI(L)2(Br)3] 3}, to assess their antipancreatic cancer activities. Complexes 1–3showed significantly greater cytotoxicity toward several pancreatic cancer cell lines with better IC50than those of the HL ligand and cisplatin. Confocal fluorescence imaging showed that complex 3was primarily localized in the mitochondria. Primarily, compound 3also can be applied to in vivoimaging. Further studies revealed that complex 3kills pancreatic cancer cells by triggering multiple mechanisms, including ferroptosis. Complex 3is the first copper complex to evoke cellular events consistent with ferroptosis in cancer cells. Finally, it significantly retarded the ASPC-1 cells’ growth in a mouse xenograft model.