Dithiocarbazate-Copper Complexes for Bioimaging and Treatment of Pancreatic Cancer

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 1–3 showed significantly greater cytotoxicity toward several pancreatic cancer cell lines with better IC50 than those of the HL ligand and cisplatin. Confocal fluorescence imaging showed that complex 3 was primarily localized in the mitochondria. Primarily, compound 3 also can be applied to in vivo imaging. Further studies revealed that complex 3 kills pancreatic cancer cells by triggering multiple mechanisms, including ferroptosis. Complex 3 is 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.