Abstract

TERPENES OF EUPHORBIA UMBELLATA LATEX ARE INVOLVED IN CYTOTOXIC EFFECT AGAINST MELANOMA CELLS

Evelyn Assis de Andrade*, Luiza Stolz Cruz, Isadora Machinski, Ana Carolina Terso Ventura, Bruna Carletto, Kátia Sabrina Paludo, Leandro Cavalcante Lipinski, Eduardo César Meurer and Flávio Luís Beltrame

ABSTRACT

Diluted latex of Euphorbia umbellata is empirically used to treat several diseases, including different types of cancer, in southern Brazil. This study aimed to evaluate the in vitro cytotoxicity of the fractions obtained from the hexane extract of E. umbellata latex; to evaluate the in vivo anticancer action of the most active fraction; and to correlate this effect with the chemical composition. The hexane extract and its fractions were tested using cytotoxic assays (MTT and neutral red) against the B16F10 cell line; the IC50 and selectivity index were determined for these samples. The most active in vitro sample of the latex was evaluated using an in vivo anticancer assay. LC-MS/MS analysis was performed to qualify and estimate the presence of the phorbol esters in the latex samples. The dichloromethane fraction presented the highest toxicity against the B16F10 cell line; the partioning process increased the cytotoxic effect and the selectivity index of the fraction obtained from the hexane extract (IC50 = 2.82 ± 0.88 μg/mL, SI = 3.4 and IC50 = 18.02 ± 1.07 μg/mL, SI = 1.1, respectively). The dichloromethane fraction did not show a significant difference regarding the volume of the tumour in relation to the tested concentrations and posology compared to the negative control. The LC-MS/MS analysis made it possible to identify phorbol esters, mainly in the dichloromethane and ethanol fractions. The ethnopharmacological use of E. umbellata latex to treat cancer may be related to the presence of terpenes in the phytocomplex of the vegetal matrix.

Keywords: Skin, diterpenes, janaúba, antitumour, phorbol esters.