Thioredoxin-1 inhibitor PX-12 induces human acute myeloid leukemia cell apoptosis and enhances the sensitivity of cells to arsenic trioxide |
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| Authors: | Yingxia Tan Laixi Bi Peili Zhang Fule Wang Feiyan Lin Wuhua Ni Jianbo Wu Lei Jiang |
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| Affiliation: | 1.Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China;2.Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China;3.Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China |
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| 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. |
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| Keywords: | PX-12 acute myeloid leukemia apoptosis arsenic trioxide |
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