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Mimic of manganese superoxide dismutase to induce apoptosis of human non-Hodgkin lymphoma Raji cells through mitochondrial pathways
Affiliation:1. Department of Pharmacy, People''s Hospital of Gansu Province, Lanzhou 730000, Gansu, China;2. Division of Oncology, People''s Hospital of Gansu Province, Lanzhou 730000, Gansu, China;1. Instituto de Investigação do Medicamento, iMed.UL, Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisboa, Portugal;2. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA;1. Department of Neurology, Third Clinical Hospital, China Three Gorges University, 60 Qiaohu 1st Road, 443002 Yichang, PR China;2. Department of Neurology, Gezhouba Central Hospital, 443002 Yichang, PR China;3. Department of Physiology, college of medical sciences, China Three Gorges University, 443002 Yichang, PR China;1. Department of Biochemistry, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand;2. Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand;3. School of Biological Sciences, University of Canterbury, Christchurch, New Zealand;1. Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, People’s Republic of China;2. Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, People’s Republic of China;3. The Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong, People’s Republic of China;1. Department of Anatomical Sciences, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran;2. Research Center of Oils and Fats, Kermanshah University of Medical Sciences, Kermanshah, Iran;3. Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran;4. Laboratorio de Desarrollo Analítico y Quimiometría (LADAQ), Catedra de Química Analítica I, Universidad Nacional del Litoral, Ciudad Universitaria, CC242 (S3000ZAA), Santa Fe, Argentina
Abstract:Increased reactive oxygen species (ROS) such as superoxide have been implicated as causal elements of oncogenesis. A variety of cancers have displayed changes in steady-state levels of key antioxidant enzymes, with the mitochondrial form of superoxide dismutase (MnSOD) being commonly implicated. Increasing MnSOD expression suppresses the malignant phenotype in various cancer cell lines and suppresses tumor formation in xenograft and transgenic mouse models. In this study, we examined the anti-proliferation effect of mimic of manganese superoxide dismutase (MnSODm) on human non-Hodgkin lymphoma Raji cells. The results showed that MnSODm significantly reduced the proliferation of Raji cells in a concentration and a time-dependent manner. By flow cytometric analysis, we found that MnSODm treatment resulted in an increased apoptosis in Raji cells. MnSODm also increased the production of ROS and the expression levels of cleaved caspase-9, caspase-3, poly (ADP-ribose) polymerase (PARP) and Bax in Raji cells. Moreover, the expression of Bcl-2 protein showed down-regulation in the MnSODm treatment group. In addition, MnSODm significantly elevated the level of cytochrome c in cytosol. These findings suggest that the activation of the mitochondrial pathway is involved in MnSODm-induced apoptosis in Raji cells.
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