Thioredoxin-interacting Protein (TXNIP) Mediates Thioredoxin-dependent Antioxidant Mechanism in Endometrial Cancer Cells Treated with 1α,25-dihydroxyvitamin D3

Abstract

Background/Aim: To determine the mechanism of vitamin D3-induced modulation of antioxidant-related factors in endometrial cancer, we investigated their role in apoptosis of human endometrial cancer cells exposed to vitamin D3. Materials and Methods: The survival rate of human endometrial cancer cells was estimated after treatment with activated vitamin D3. Reactive oxygen species (ROS) levels were measured using flow cytometry. The levels of VDR, Trx, TXNIP and apoptosis-related proteins were investigated using western blotting and immunocytochemistry in human tissues. Results: Treatment with D3 induced apoptotic cell death and cell-cycle arrest by increasing ROS concentration. Vitamin D3 inhibited proliferation of human endometrial cancer cells. It regulated intracellular ROS concentration in endometrial cancer cells via increased TXNIP expression. Conclusion: Antioxidant regulation via TXNIP is an important cell death mechanism in human endometrial cancer, and occurs via induction by vitamin D3