80:41928-39; PMID:16223732; http://dx.doi.org/10.1074/jbc. M

Int J Clin
80:41928-39; PMID:16223732; http://dx.doi.org/10.1074/jbc. M
Int J Clin Exp Pathol 2014;7(8):4765-4773 www.ijcep /ISSN:1936-2625/IJCEPOriginal Article Thioredoxin-1 inhibitor PX-12 induces human acute myeloid leukemia cell apoptosis and enhances the sensitivity of cells to arsenic trioxideYingxia Tan1*, Laixi Bi2*, Peili Zhang1, Fule Wang1, Feiyan Lin1, Wuhua Ni3, Jianbo Wu1, Lei JiangLaboratory of Internal Medicine, The very first Affiliated Hospital of Wenzhou Healthcare University, Wenzhou, Zhejiang 325000, China; 2Department of Hematology, The first Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; 3Reproductive Medicine Center, The first Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. *Equal contributors.Received June 26, 2014; Accepted August 2, 2014; Epub July 15, 2014; Published August 1, 2014 Abstract: Thioredoxin-1 (Trx-1), a vital redox regulatory element, plays a considerable function in drug-induced apoptosis. Here we investigated the effects on the Trx-1 inhibitor 1-methylpropyl 2-imidazolyl disulfide (PX-12) on human acute myeloid leukemia cells (AML) along with the sensitivity of cells to arsenic trioxide (As2O3, ATO). Treatment of cells using a distinct concentration of PX-12 for 48 h resulted in development inhibition, the induction of apoptosis and improved the levels of activated caspase-3 expression in AML cell lines HL-60, NB4, U937 and main AML cells within a dose-dependent manner. Additionally, PX-12 enhanced the sensitivity of U937 cells to ATO. These outcomes suggest the effects of Trx-1 inhibitor PX-12 to induce apoptosis in AML cells and therapeutic possible in AML by enhancing the sensitivity of cells to ATO. Keywords: PX-12, acute myeloid leukemia, apoptosis, arsenic trioxideIntroduction Acute myeloid leukemia (AML) is usually a clonal disorder characterized by a disruption in typical hematopoietic differentiation along with the accumulation of abnormal, immature myeloid cells within the bone marrow, resulting in hematopoietic failure [1]. AML is definitely the most typical acute leukemia affecting adults and its incidence rises drastically with age. Despite recent advancements, treatment of AML remains unsatisfactory [2]. Arsenic trioxide (As2O3, ATO), an ancient conventional Chinese medicine, has been reported to become an efficient therapeutic agent for acute promyelocytic leukemia (APL) [3, 4]. ATO induces apoptosis and partial differentiation in a assortment of leukemia cells, suggesting that it may be effective against other hematologic malignancies [5].Ethyl cinnamate Formula Having said that, ATO employed as a single agent at greater concentrations causes quite a few negative effects, cytotoxicity and drug resistance are important concern [6, 7].Boc-D-Lys-OH Autophagy A lot more recently it has been shown to be effective, particularly in mixture with other drugs within the remedy of leukemia [7-9].PMID:23626759 The thioredoxin (Trx) method is one of the major cellular antioxidant technique integral to keeping the intracellular redox state [10]. Trx-1 that is principally localized in the cytoplasm and Trx-2 which is mostly localized in the mitochondria, suggests their particular effects in diverse cellular compartments [11]. Trx-1, a 12-kDa ubiquitous protein that has disulfide-reducing activity and protects cells against oxidant harm, is one particular member from the Trx system. Accumulating proof indicates that Trx-1 plays an important role in tumor progression and metastasis. Elevation of Trx-1 expression increases cancer cell proliferation, inhibites apoptosis and aggressive tumor g.