Atividade anticâncer da Biflorina em células tumorais gástricas

Abstract

In the northern Brazil, especially in the states of Amazonas and Pará, there is a high incidence of gastric cancer which available treatments are ineffective in most cases. The biflorin, a prenylated ortanaftoquinona obtained from the roots of Capraria biflora L., showed, in previous studies, an inhibition of the tumor growth in vivo and in vitro in several cell lines, without inducing mutagenicity. The ACP02, main cell line used in this work, was established from a primary diffuse gastric adenocarcinoma, removed from the stomach cardia region of a 66-year-old pacient born in Pará. Among the main karyotypes and genetic changes of this lineage are the trisomy of chromosome 8, with amplification of the MYC oncogene, and the deletion of the chromosome 17’s short arm, where the tumor suppressor gene TP53 is located. These characteristics observed in the established line correspond to those observed in the original tumor, what indicates that this line is a good alternative to the study of the human gastric cancer pathophysiology and the drug screening. Considering biflorin’s promising potencial and the necessity to regionalize the study of new anticancer drugs to answer genotype particularities of each group of patients, we evaluated the activity of biflorin on ACP02 through the morphological cell analysis, the cell viability assays, the clonogenic assay, scratch assay, the cell differentiation test by NBT, the evaluation of the MYC status and telomere length by FISH, in 0, 1.0, 2.5 and 5.0 M concentrations, after 24 and 72 hours of treatment. The morphological changes indicate cell death by necrosis, and suggest the occurrence of the differentiation process, due to change in the format of the attached cell. The biflorin showed a cytotoxic activity (IC50 1.92 M) and cytostatic, anticlonogenic and antimotility activities, statistically significant (p<0,05) since 1 M. There was a significant reduction in MYC amplification rate in cells treated with 2.5 e 5 M of the drug (p<0,05), which can explain the occurrence of cellular differentiation process, in view of the physiological role of this gene. This differentiation was confirmed by the results obtained during the NBT test, in which the cells showed the ability to metabolize salt from a treatment of 1.0 M. The telomere length was reduced in cells treated with 5.0 M of biflorina (p<0,05). These results showed that biflorin acts on important targets of anticancer therapy, when used on the gastric line ACP02, at concentrations around 2.5 M, which makes it a promising substance for the treatment of this tumor type.