Thioredoxin-1 inhibitor, 1-methylpropyl 2-imidazolyl disulfide, inhibits the growth, migration and invasion of colorectal cancer cell lines

Abstract

1-Methylpropyl 2-imidazolyl disulfide (PX-12) has been proposed as an inhibitor of thioredoxin-1 (Trx-1) with antitumor activity. However, the antitumor activity of the Trx-1 redox signaling inhibitor PX-12 on colorectal cancer is still obscure. In the present study, we showed that PX-12 inhibited the growth of colorectal cancer DLD-1 and SW620 cells in a dose-and timedependent manner. Further analysis demonstrated that PX-12 reduced cell colony formation and induced a G2/M phase arrest of the cell cycle. In addition, PX-12 treatment induced apoptosis, as observed by the increased number of Annexin V-positive cells and increased activation of caspase-3. Notably, a low dose of PX-12 inhibited colorectal cancer cell migration and invasion. Treatment of cancer cells with PX-12 reduced NOX1, CDH17 and S100A4 mRNA expression, and increased KLF17 mRNA expression. Moreover, PX-12 decreased S100A4 protein expression in the colorectal cancer cells. Collectively, the present study demonstrates the antitumor effects and therapeutic potential of PX-12 in colorectal cancer.