Ascorbic acid recycling in Nb2 lymphoma cells: implications for tumor progression |
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| Institution: | 1. Department of Physiology, University of North Dakota School of Medicine, Grand Forks, ND, USA;2. Department of Pharmacology & Toxicology, University of North Dakota School of Medicine, Grand Forks, ND, USA;3. Department of Cancer Endocrinology, British Columbia Cancer Agency, Vancouver, BC, Canada;1. Laboratório de Cultura Celular, ICB, FURG, RS, Brazil;2. Programa de Pós-Graduação em Ciências Fisiológicas, ICB, FURG, RS, Brazil;3. Escola de Química e Alimentos, EQA, FURG, RS, Brazil;4. Centro de Ciências Computacionais, FURG, RS, Brazil;5. Centro de Biotecnologia, Universidade Federal da Paraíba, PB, Brazil;6. Universidade Federal do Pampa, Campus São Gabriel Brazil;1. Department of Radiation Biology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken 980-8575, Japan;2. Department of Radiation Oncology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken 980-8575, Japan;1. Seiwa Kasei Co., Ltd., 1-2-14, Nunoichicho, Higashiosaka, Osaka 579-8004, Japan;2. Tokyo University of Technology, 1404-1, Katakuracho, Hachiouji, Tokyo 192-0982, Japan;1. Department of Pharmacology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea;2. Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 120-749, Republic of Korea;1. Department of Infectious Diseases, St. Jude Children''s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA;2. Department of Immunology, St. Jude Children''s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA;3. Department of Pediatrics, University of Tennessee Health Sciences Center, 50 North Dunlap Street, Memphis, TN 38103, USA |
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| Abstract: | Analysis of cultured rat “Nb2 lymphoma” cell lines, showing different degrees of malignant progression, can lead to identification of phenotypic changes associated with this phenomenon in T-cell cancers. In the present study we have compared the metastatic sublines, Nb2-11 and Nb2-SFJCD1, with regard to ascorbate and glutathione recycling, important processes in cellular protection from oxidative stresses. Whereas the Nb2-11 subline is prolactin (PRL)-dependent, the genetically related Nb2-SFJCD1 subline is growth factor-independent and shows more chromosomal alterations, indicative of more advanced progression. The Nb2-SFJCD1 cells, compared to the Nb2-11 cells, were less sensitive to toxic effects of dehydroascorbate, a potentially toxic oxidation product of ascorbate. Results were consistent with a significantly higher production of reducing equivalents (e.g., NADPH, GSH) and an accelerated reduction of dehydroascorbate by homogenates of Nb2-SFJCD1 cells. However, the increased resistance was apparently not directly related to the cellular uptake and reduction of dehydroascorbate by whole cells, which was similar in both cell lines. Observations indicate that Nb2 lymphoma cells, in their progression to malignancy, can acquire an enhanced capability to protect themselves from oxidative damage assisting them in withstanding the oxidative stress that anti-neoplastic drugs can cause. The adaptation may also be a mechanism that is utilized by tumor cells in suppressing apoptosis and other protective cellular functions facilitating, or potentiating, a tumor cell’s ability to become more metastatic. However, the mechanism leading to this augmented capacity of Nb2 lymphoma cells to resist oxidative stress in not known and is the subject for further study. |
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