title: 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.
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, Zhejiang 325000, China.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, Zhejiang 325000, China.
authors.forename: Laixi
authors.initials: L
authors.lastname: Bi
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, Zhejiang 325000, China.
authors.forename: Peili
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, Zhejiang 325000, China.
authors.forename: Fule
authors.initials: F
authors.lastname: Wang
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, Zhejiang 325000, China.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Lin
authors.affiliation: Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, Zhejiang 325000, China.
authors.forename: Wuhua
authors.initials: W
authors.lastname: Ni
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, Zhejiang 325000, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wu
authors.affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University Wenzhou, Zhejiang 325000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000494:pharmacology*; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute; D010087:Oxides / Q000494:pharmacology; D013879:Thioredoxins / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D004220:Disulfides; D007093:Imidazoles; D010087:Oxides; C491203:TXN protein, human; D013879:Thioredoxins; C412893:1-methylpropyl-2-imidazolyl disulfide; D000077237:Arsenic Trioxide
keywords: PX-12; acute myeloid leukemia; apoptosis; arsenic trioxide