AVALIAÇÃO DA ATIVIDADE ANTITUMORAL IN VITRO DE EXTRATOS DE Crinum scabrum E DO ALCALOIDE CRINAMINA EM LINHAGENS LEUCEMICAS E MELANOMA

Abstract

Cancer is one of the most important health problems today, being one of the main causes of death in the world, with an increasing incidence. Faced with this scenario, the scientific community has made efforts to seek alternatives that alleviate the problem, such as the search for new therapeutic possibilities, treatments and active compounds. Within this search, plants have been a promising alternative, due to the wide variety of active substances. The family Amaryllidaceae has been the target of studies due to the presence of several alkaloids with biological activity, where potential antitumor effects have been observed in some species. Although there are some studies on the family, there are still unstudied species, such as Crinum scabrum. The aim of this study was to evaluate the antitumor activity of the species in vitro. To this end, the crude extract, methanolic extract and ethyl acetate fraction, as well as the isolated alkaloid crinamine, were tested in a cell viability assay with dye resazurin on cell lines K562 (chronic myeloid leukemia), KG1 (acute myeloid leukemia) and B16F10 (melanoma). The strains were added to 96-well plates at a density of 1x10e4, followed by the addition of the extracts and alkaloid and incubated for 48 hours at 37°C and 5% CO2. Readings were taken on a spectrophotometer at wavelengths of 570 and 600nm. Cells of the NIH/3T3 lineage (mouse fibroblasts) were used as the non-tumor control, the antineoplastic drug doxorubicin was used as a death control (CM), and cells in culture medium were used as a life control (CV). To better interpret the results, the inhibitory and cytotoxic concentrations for 50% of the cells (CI50 and CC50) were calculated using non-linear regression with the aid of the GrandPad Prism 5.0 program. The selectivity index was calculated as the ratio of CC50 to CI50. Among the compounds tested, the methanolic extract and crinamine showed the best results, reducing the cell viability of the KG1 and K562 lines with a high selectivity index (177,94 and >23,25 for the extract; and 287,35 and 79,43 for crinamine) and low cytotoxic action in the mouse fibroblast line (NIH/3T3) (CC50 >1000 μg/ml and >1000μM, respectively for the extract and crinamine), showing promise for further studies as therapeutic alternatives. In addition, studies on the more detailed phytochemical characterization of the species, as well as the identification of substances that may be associated with the antitumor activity observed, the molecular targets involved and the probable mechanism of action, should also be evaluated in future work.