Dysregulated calcium homeostasis and oxidative stress in chronic myeloid leukemia (CML) cells |
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| Authors: | Roberto Ciarcia Danila d'Angelo Carmen Pacilio David Pagnini Massimiliano Galdiero Filomena Fiorito Sara Damiano Eliseo Mattioli Chiara Lucchetti Salvatore Florio Antonio Giordano |
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| Institution: | 1. Department of Structures, Functions and Biological Technologies, School of Veterinary Medicine, University of Naples “Federico II”, Naples, Italy;2. Department of Medical Oncology C INT, Foundation G. Pascale, Naples, Italy;3. Director U.O. Haemathology, ASL Caserta (CE), Hospital Praesidium, San Felice a Cancello, Caserta, Italy;4. Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy;5. Department of Pathology and Animal Health, School of Veterinary, Medicine University of Naples “Federico II”, Naples, Italy;6. Department of Human Pathology & Oncology, University of Siena, Siena, Italy;7. Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania |
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| Abstract: | Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder caused by the oncogenic activity of the Bcr‐Abl protein, a deregulated tyrosine kinase. Calcium may act directly on cellular enzymes and in conjunction with other cellular metabolites, such as cyclic nucleotides, to regulate cell functions. Alteration in the ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation as well as the production of reactive oxygen species (ROS) has been correlates with normal cell proliferation through activation of growth‐related signaling pathways. In this study we evaluated in peripheral blood leukocytes from CML patients the role of the balance between intracellular calcium and oxidative stress in CML disease in order to identify possible therapeutic targets in patients affected by this pathology. Our results demonstrated that peripheral blood mononuclear cells derived from CML patients displayed decreased intracellular calcium Ca2+]i fluxes both after InsP3 as well as ATP and ionomycin (IONO) administration. CML cells showed lower levels of superoxide dismutase (SOD) activity and significantly higher malondialdehyde levels (MDA) than peripheral blood mononuclear cells derived from control patients. Finally we showed that resveratrol is able to down‐regulate InsP3 and ATP effects on intracellular calcium Ca2+]i fluxes as well as the effects of ATP and IONO on oxidative stress in CML cells. J. Cell. Physiol. 224: 443–453, 2010. © 2010 Wiley‐Liss, Inc. |
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