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Parthenolide Reduces Gene Transcription of Prosurvival Mediators in U937 Cells Publisher Pubmed



Mohammadi S1 ; Zahedpanah M2 ; Nikbakht M1 ; Shaiegan M3 ; Hamidollah Ghaffari S1 ; Nikugoftar M3 ; Rahmani B4 ; Hamedi Asl D4
Authors
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Authors Affiliations
  1. 1. Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, 14176-13151, Iran
  2. 2. Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, 34157-38477, Iran
  3. 3. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, 14665-1157, Iran
  4. 4. Department of Biochemistry and Genetics, Qazvin University of Medical Sciences, Qazvin, 34157-38477, Iran

Source: Experimental Oncology Published:2017


Abstract

In acute myeloid leukemia (AML) the functional abnormalities of osteopontin (OPN), NF-kB, PI3K/AKT/mTOR/PTEN pathway or β-catenin have been considered. Aim: To analyze the response of U937 cells to parthenolide (PTL) through the involvement of expression of OPN protein, RelB, AKT1, mTOR, PTEN and β-catenin genes. Materials and Methods: The U937 cells were treated with PTL at concentrations of 4 μM (IC25) or 6 μM (IC50) and with OPN siRNA for MTT assay and colony forming assay. Western blot analysis using antibodies against OPN was performed with lysates of PTL-treated cells. Quantitative real-time polymerase chain reaction was performed using primers for OPN siRNA, RelB, AKT1, mTOR, PTEN and β-catenin. Results: PTL reduces OPN protein level and down-regulates RelB mRNA in U937 cell line. Suppression of OPN with siRNA increases the cytotoxic effects of PTL. Also, mRNA expression of AKT1, mTOR, PTEN, and β-catenin decreases with PTL or OPN siRNA. Conclusion: Sensitivity of U937 cells to PTL can be associated with the reduction in expression of prosurvival mediators.