Down-regulation of Bcl2 and Survivin,and up-regulation of Bax involved in copper (II) phenylthiosemicarbazone complex-induced apoptosis in leukemia stem-like KG1a cells |
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| Affiliation: | 1. Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran;2. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;1. Deparment of Chemistry and Chemical Processing Technologies, Mersin University, 33343, Mersin, Turkey;2. Deparment of Chemistry and Chemical Processing Technologies, Dicle University, 21280, Diyarbakır, Turkey;3. Food Processing Programme, Mersin University, 33343, Mersin, Turkey;4. Deparment of Chemistry and Chemical Processing Technologies, Siirt University, 56100, Siirt, Turkey;5. Chemistry Department, Sciences Faculty, Erciyes University, 38039, Kayseri, Turkey;6. Technology Research & Application Center (TAUM), Erciyes University, 38039, Kayseri, Turkey;1. Microbial Engineering Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India;2. Systems Biology for Biofuel Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India;3. DBT-ICGEB Centre for Advanced Bioenergy Research, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India;4. DBT-ICT Centre for Energy Biosciences, Institute of Chemical Technology, Mumbai 400019, India;1. Division of Urology, Department of Surgery, the Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada;2. Ottawa Hospital Research Institute, Ottawa, Ontario, Canada;3. University Health Network, Toronto, Ontario, Canada;4. University of Western Ontario, London, Ontario, Canada;5. QEII Health Sciences Centre, Halifax, Nova Scotia, Canada;6. McGill University, Montreal, Quebec, and University of Alberta, Edmonton, Alberta, Canada;1. Swedish Centre for Resource Recovery, University of Borås, 501 90, Borås, Sweden;2. The Flemish Institute for Technological Research, VITO NV, Boeretang 200, B-2400, Mol, Belgium;3. Department of Chemical Engineering, Amirkabir University of Technology, 15875-4413, Tehran, Iran;4. Mixed Matrix Material Innovations BVBA, B-2160, Wommelgem, Belgium |
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| Abstract: | Previous studies suggested that phenylthiosemicarbazones are considered as a new apoptosis-inducing agent. In this study, anti-proliferative and apoptotic effects of the copper (II) phenylthiosemicarbazone complex (Cu-PTSC) were investigated in human acute myeloid leukemia KG1a cell line. The KG1a cells were treated with various concentrations (20−140 μM) of the Cu-PTSC, and cell viability was determined by MTT assay. The IC50 value of 80 ± 2.5 μM was selected for further evaluations. Apoptosis, as the antitumor strategy in the cells, was investigated morphologically by acridine orange/ethidium bromide (AO/EtBr) double staining, and surface expression assay of phosphatidylserine by Annexin V/PI technique was studied via flow cytometry. Results indicated that the cells undergo morphologic changes with chromatin condensation and G0/G1 cell cycle arrest after treatment with Cu-PTSC. The presence of phosphatidylserine on the outer surface of the cell membrane confirmed the apoptosis occurrence in the KG1a cells. Real-time PCR and western blot analyses revealed that the incubation of KG1a cells with Cu-PTSC down-regulated the expression of Bcl-2 (anti-apoptotic protein) and Survivin (as an IAP protein) while induced the expression of Bax (pro-apoptotic protein). Based on present data, it seems that Cu-PTSC may provide a novel therapeutic approach for the treatment of acute myeloid leukemia. |
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| Keywords: | Apoptosis Cu-PTSC Bax Bcl-2 Survivin KG1a cell line |
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