Thioredoxin-interacting Protein (TXNIP) Mediates Thioredox-independent Antioxidant Mechanism in Endometrial Cancer Cells Treated With 1 alpha,25-dihydroxyvitamin D-3

Abstract

Background/Aim: To determine the mechanism of vitamin D-3-induced modulation of antioxidant-related factors in endometrial cancer, we investigated their role in apoptosis of human endometrial cancer cells exposed to vitamin D-3. Materials and Methods: The survival rate of human endometrial cancer cells was estimated after treatment with activated vitamin D-3. 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 D-3 induced apoptotic cell death and cell-cycle arrest by increasing ROS concentration. Vitamin D-3 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 D-3.