S Mohammadi1, M Zahedpanah2, M Nikbakht1, M Shaiegan3, Ghaffari Hamidollah1, M Nikugoftar3, B Rahmani4, D Hamedi Asl4. 1. Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran 14176-13151, Iran. 2. Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin 34157-38477, Iran. 3. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran 14665-1157, Iran. 4. Department of Biochemistry and Genetics, Qazvin University of Medical Sciences, Qazvin 34157-38477, Iran.
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.
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.
Authors: Akram Mirzaei; Saeed Mohammadi; Seyed H Ghaffari; Marjan Yaghmaie; Mohammad Vaezi; Kamran Alimoghaddam; Ardeshir Ghavamzadeh Journal: Asian Pac J Cancer Prev Date: 2018-03-27