Page 26 - D. Cancer biology

[D. Cancer biology-20]

Broad anti-cancer effect of a specific thioredoxin reductase 1

inhibitor

Eunkyu Sung¹, Sang Won Kang¹˙*

¹Life Science, Ewha Womans University, Seoul 03760, South Korea

Thioredoxin (Trx) system is one of the antioxidant systems that maintains the balance of reactive oxidant species
(ROS) level. In both normal and cancerous cells, ROS are produced as the by-product of aerobic metabolism. Lower
level of ROS supports proliferation and survival pathways, and thus serves as signaling molecules to regulate

biological processes. However, a higher level of ROS can damage DNA, proteins and lipids, which causes senescence

and cell death. As a coupling enzyme, TrxR is particularly interesting because it is highly expressed in liver, lung and
other cancers. Although many TrxR inhibitors such as auranofin were developed, these inhibitors target not only
cytosolic but also mitochondrial TrxR. Inhibition of mitochondrial TrxR influences mitochondrial function. In this

study, we examined that new inhibitor (225-C8) specifically targets the cytosolic TrxR to suppress cancer cell growth.
We found that 225-C8 properly functions in cells by decreasing TrxR1 activity in cancer cells, which correlates with

the cancer cell cytotoxicity. These results demonstrate that selectively suppressing cytosolic TrxR can inhibit cancer
cell growth, which is expected to work for anti-cancer therapy.