Thioredoxin-1 inhibitor PX-12 induces human acute myeloid leukemia cell apoptosis and enhances the sensitivity of cells to arsenic trioxide.

Abstract

Thioredoxin-1 (Trx-1), an important redox regulatory factor, plays a significant role in drug-induced apoptosis. Here we investigated the effects of the Trx-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) on human acute myeloid leukemia cells (AML) and the sensitivity of cells to arsenic trioxide (As2O3, ATO). Treatment of cells with a different concentration of PX-12 for 48 h resulted in growth inhibition, the induction of apoptosis and increased the levels of activated caspase-3 expression in AML cell lines HL-60, NB4, U937 and primary AML cells in a dose-dependent manner. In addition, PX-12 enhanced the sensitivity of U937 cells to ATO. These results suggest the effects of Trx-1 inhibitor PX-12 to induce apoptosis in AML cells and therapeutic potential in AML by enhancing the sensitivity of cells to ATO.