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Assessing the potential use of Extracellular ATP against leukemic lineage

Grant number: 11/15615-5
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2012
Effective date (End): February 28, 2014
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Edgar Julian Paredes-Gamero
Grantee:Antonio Carlos Ribeiro Filho
Home Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil

Abstract

Among the hematological cancers that occur by altering of proliferation and differentiation mechanisms we can found the leukemias. Did not exist an efficient treatment again leukemias. The inefficiency is due to the current treatment against cancer is mainly directed again cells with high proliferation rate. However, the present of a rare population of leukemic cells, with characteristics of stem cells, called leukemic stem cells (CTL), has been described. This rare leukemic population possesses hematopoietic stem cells features such as unlimited self-renewal and low rate of proliferation. Among the strategies against leukemia are drugs with potential for differentiation as ATRA and interferon-a. In recent years, our group has shown the ability to differentiate ATP, which activates P2 receptors (ionotropic and metabotropic), mainly in the population of hematopoietic stem cells, using in vitro and in vivo models (Paredes-Gamero et al. 2008; Barbosa et al., 2011). Thus, the aim of this project is explore the antitumor ability of ATP and analogs in leukemic lineages such as K562 and HL-60, evaluating mainly the most primitive component in these lineages. We will quantified this primitive population, investigate its clonogenic capability and cell viability after treatment with ATP. We also will identify the likely receptor activated by ATP and the participation of intracellular Ca2+ via, which it is main pathway activated by purinergic receptors.