A citotoxicidade do Cloreto de Cobalto (CoCl2) em células leucêmicas é célula dependente: estudo dos mecanismos envolvidos neste processo

Abstract

Cobalt is a transition metal essential for human health that plays a critical role in the synthesis of vitamin B12. Historically, inorganic cobalt was used in the treatment of anemia and chronic renal failure and, afterwards, to mimic hypoxia, associating its effects with the activation of HIF-1α. Lately, CoCl2 attracted attention in cancer research because of its antiproliferative potential, which may involve HIF-1αindependent mechanisms, still poorly understood. In this study, we evaluated the antiproliferative effect of CoCl2 in leukemic cells lineages (JURKAT, U937 and K562) and the mechanisms involved in this process. To test the possible antiproliferative effect of CoCl2 in neoplastic cells, we analyzed the viability and cell cycle by flow cytometry using as probe Propidium Iodide and to confirm apoptosis use YO-PRO-1 more Propidium Iodide to perform testing by the difference in membrane permeability/dead cell. ROS levels were detected by probe DCFH-DA oxidation and the levels of the transcription factor NF-kB and its possible activation were detected by Western Blot in nuclear and cytoplasmic fractions, the levels of β-actin was used as control. The three lineages showed increased levels of ROS and cell cycle arrest in G2 phase when subjected to treatment with CoCl2. Only JURKAT e U937 undergone apoptosis and showed significant decreases in NF-kB expression after 24h of CoCl2 treatment. Differentially, K562 cells maintained NF-kB levels. Our data suggest that CoCl2 induces cell death may be related to a balance between stress responses and maintenance of NF-kB expression.