Anticancer and Antiangiogenic Iron(II) Complexes That Target Thioredoxin Reductase to Trigger Cancer Cell Apoptosis

Thioredoxin
reductase (TrxR) is a selenoenzyme that could regulate
intracellular oxidative balance and found to be overexpressed in many
human tumor cells. Due to its important role in cancer progression,
TrxR is becoming an attractive target in chemotherapeutic drug design.
In this study, a new class of Fe­(II) complexes with phenanthroline
derivatives as ligands were synthesized and characterized. The mechanism
of cell death induced by complex 3 revealed that the
growth of cancer cells was suppressed by apoptosis and specifically
inhibited the activities of TrxR. Furthermore, complex 3 exhibited brilliant antiangiogenic activity against HUVEC cells
and inhibited cell migration and invasion. In addition, results of
hematological analysis and H&E staining demonstrated that complex 3 has negligible toxicity on function of the major organs
of mice. Taken together, this study provides a strategy for drug design
to exploit Fe-based phenanthroline derivative as a chemotherapeutic
agent in cancer treatment.