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.