Investigação da mielotoxicidade e do potencial indutor de morte celular de Synadenium umbellatum Pax. em células do tumor ascítico de Ehrlich
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2010-03-03
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Universidade Federal de Goiás
Resumo
In search of new antineoplasic agents natural products have played an important role,
given that about 40% of available medicines in current treatments have been developed
from natural sources, 25% approximately of plants. Synadenium umbellatum belongs to
Euphorbiaceae family and is popularly known as "cola-nota", "avelós," "milagrosa",
"cancerola", and the latex is empirically used in Brazil for the treatment of cancer.
Preliminary studies have shown that the crude extract of the leaves of S. umbellatum
has significant antitumor and antiangiogenic activity in vivo. In this study, we
investigated the cytotoxicity and the mechanisms of apoptosis induction of S.
umbellatum in Ehrlich ascitic tumor (EAT) cells, and the myelotoxic potential of this
plant. The cytotoxicity studies were carried out by trypan blue exclusion and reduction of
tetrazolium (MTT) tests. The mechanisms of apoptosis induction were investigated by
light and fluorescence microscopy, immunocytochemistry and flow cytometry.
Investigation of the myelotoxic potential was performed by clonogenic assay of colony
forming units of granulocyte-macrophage (CFU-GM). The data were analyzed by
analysis of variance (ANOVA) and a posteriori Tukey test (myelotoxicity) and by t test for
all other assays. The means were considered statistically significant when P < 0.05. S.
umbellatum was cytotoxic to EAT cells and the morphological analysis of these cells
indicated that the plant extract treatment induced cell death by apoptosis. Apoptosis was
also observed by increase on reactive oxygen species generation and in the
concentration of intracellular Ca2+, alterations in mitochondrial membrane potential,
phosphatydylserine externalization and activation of caspases 3, 8, and 9. S.
umbellatum presented myelotoxicity to normal bone marrow cells in a concentrationdependent
fashion. However, this toxicity was 8-fold lower than to tumor cells. The
presented data showed that S. umbellatum had cytotoxic activity to EAT cells and
induced these cells to apoptosis.
Descrição
Palavras-chave
Citotoxicidade , Synadenium umbellatum , mielotoxicidade , morte
celular , apoptose , Tumor ascítico de Ehrlich , Synadenium umbellatum , cytotoxicity , cell death , apoptosis , myelotoxicity , Ehrlich ascitic tumor , 1. Citotoxicidade 2. Synadenium umbellatum 3.
Mielotoxicidade 4. Morte celular 5. Apoptose 6. Tumor
ascítico de Ehrlich
Citação
MOTA, Mariana Flávia da. Investigation of myelotoxicity and potential inducer
cell death of Synadenium umbellatum Pax. cell
Ehrlich ascites tumor. 2010. 86 f. Dissertação (Mestrado em Ciências da Saúde - Farmácia) - Universidade Federal de Goiás, Goiânia, 2010.