Navegando por Palavras-chave "Leukemias"

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    Beta carbolinas: estudo dos mecanismos de morte, proliferação e diferenciação em leucemias e células-tronco leucêmicas
    (Universidade Federal de São Paulo (UNIFESP), 2018-10-25) Torquato, Heron Fernandes Vieira [UNIFESP]; Gamero, Edgar Julian Paredes [UNIFESP]; http://lattes.cnpq.br/9562213378846769; http://lattes.cnpq.br/7439686090439905; Universidade Federal de São Paulo (UNIFESP)
    Acute myeloid leukemia ( AML) is a type of cancer that occurs from the clonal expansion of myeloid pr ecursors. Over the past few years, a hypothesis used to explain the leukemia origin has been the presence of a rare population inside of the tumor, which represents a refractory reservoir to therapy, named leukemic stem cell (LSC). For this reason, the elimination of this population is considered an important treatment method nowadays. Among all natural products that have provided new molecules with different clinical applications, we highlight the betacarbolinic alkaloids, in particular, the canthinone and its derived, which have demonstrated diverse pharmacological activities s uch as antibacterial, antifungal, antimalarial, antiulcerogenic and cytotoxic. Thus, the aim of this project was to investigate the antitumor effects of betacarbolinic alkaloids in leukemias and in the LSC population. Therefore, the effects of betacarboline alkaloids on cell death, proliferation and differentiation were investigated. It was observed that the effect on cell death occurred by apoptosis ( dissipation of mitochondrial potential, permeabilization of lysosomes, production of reactive oxygen species [ROS], and activation of caspases) and by Necroptosis ( use of pharmacological inhibitors of necroptosis, Nec1 and necrosulfonamide, as well as their association with caspase inhibitors). In addition, a cytostatic effect with cell cycle ar rest in the G2/M phase associated by activation of DNA damage sensor proteins and the decrease of clonogenic capability was observed. Induction of cell differentiation was also observed by expression increased of myeloid differentiation markers ( CD15, C D11b, C D14, P U.1 and MPO). The differentiation also affected LSC population with expression increase of PU.1 factor, and proliferation increase, but the reduction of clonogenic potential. Part of the effects on differentiation and proliferation was blocked by the p38 inhibitor, SB203580. The results show important actions of this metabolites class, highlighting the effects of MTXc as privileged structures for the construction of new antileukemic drugs