Avaliação do potencial citotóxico de extratos de Euphorbia umbellata (Pax) Bruyns

Abstract

Cancer is a large group of diseases characterized by uncontrolled cell growth in several parts of the body. It is a public health issue given its high mortality rates, and thus, the search for new drugs for treatment of this issue is necessary. In this way, the sap of Euphorbia umbellata (Pax) Bruyns is popularly used, in a dilution, for cancer treatment and there are evidences in the literature of its in vitro e in vivo antitumor effect. In this study it was analyzed the cytotoxic potential of fractions, subfractions and euphol, an isolated substance of this plant matrix. For this, five cell lineages were used, a model of leukemia (K-562), two models of colorectal cancer (HT-29 and HCT 116) and two models of breast cancer (MCF-7 and MDA-MB 231). The cytotoxic potential was determinate from cell viability, using MTT reduction assay. The IC50 (inhibitory concentration 50%) and the selectivity indices (SI) were calculated, the last in relation to non-plastic cells. In addition, possible mechanisms associated to the cytotoxic effect were evaluated. Morphology and cell cycle analysis were performed for HL-60 and K-562 cells, and activation of caspases 3 and 7 was evaluated in MDA-MB 231 and HL-60 cells. The hexane fraction showed IC50 value of 7.78 μg/mL, meanwhile, between the subfractions evaluated, the best was ethanol subfraction with IC50= 1.26 μg/mL, euphol was also cytotoxic with IC50= 34.44 μM, to K-562 cells. The selectivity assay revealed that dichloromethane subfraction is selectivity compared with lymphocytes and monocytes, with values ranging of 7.42 and 9.11, respectively, on the other hand, euphol present selectivity parameter up to 2.35. The dichloromethane and ethanol subfractions, and euphol were able to activate caspases 3 and 7, to alter the cell morphology and cycle on HL-60 and K-562 cells. While, for the other cells only the methanol fraction was not able to reduce the cell viability by more than 50%. The lowest IC50 (7.77 μg/mL) was obtained with MDA-MB 231 cells after of treatment with ethyl acetate fraction. The subfractions were also cytotoxic to the colorectal and breast cancer cells, the MDA-MB 231 was the most sensitive cell to the treatment with dichloromethane subfraction (IC50= 16.76 μg/mL). Euphol was cytotoxic to all the cell lines, with the lowest IC50 value of 12.38 μM to the MDA-MB 231 cell. In comparison with the non-plastic cell lineage, HEK-293, the ethyl acetate fraction was the most selective with IS= 9.85 for MDA-MB 231 cells and euphol showed a selectivity index of 6,47 for the same cell line. The treatments with ethyl acetate fraction, dichloromethane subfraction and euphol were able to activate caspases 3 and 7 in MDA-MB 231 cells. Thus, plant matrices obtained from E. umbellata latex have cytotoxic potential, as well as the isolated compound, euphol, and that this action is induced by apoptosis.