Bioprospecção da geoprópolis de Melipona fasciculata Smith: estudo químico e avaliação da atividade antitumoral em linhagens de câncer de pulmão

Abstract

The stingless bee Melipona fasciculata Smith (tiúba) accumulates pollen and produces honey, wax and geopropolis, which is a mixture of plant resins, salivary secretions,

wax and earth/or clay. Geopropolis has proven biological activities, such as anti- inflammatory, antioxidant, antimicrobial, healing, leishmanicidal, immunomodulatory

and anthelmintic. However, there is a lack of references to anti-cancer actions of the geopropolis of the species. Considering that worldwide, lung cancer has high mortality, and conventional cancer treatment drugs have been showing resistance, it is important to search for new substances from natural products. Thus, the research aimed to make a bibliographic review of pre-clinical studies of propolis and geopropolis of stingless bee species in the area of cancer and bioprospecting studies of geopropolis from Melipona fasciculata Smith in an in vitro evaluation model of activity in cells of lung cancer, as well as chemical identification of bioactive subfractions. The geopropolis samples of tiúba were collected in a meliponary in the city from Viana, Maranhão, which were dried, tritured and extracted by maceration with 70% ethanol, obtaining. hydroethanolic extract of geopropolis and later lyophilized (EHGV). EHGV was subjected to liquid-liquid partition, obtaining the hexane (HF), ethyl acetate (EAF) and hydromethanolic (HMF) fractions. Biodirected fractionation of EAF by column chromatography resulted in 13 subfractions (FRGE-1 to FRGE-13). Bioactive subfractions were identified by LC and LC–ESI/IT–EM/MS. The in vitro cytotoxicity of fractions and subfractions was evaluated in lung cancer cell lines (H460 and A549) and normal cells (HUVEC) by the 3-4,5-dimethylthiazol-2,5-diphenyl bromide (MTT) assay and the determined selectivity indices. The results of the literature review are published in the journal Pharmaceuticals 2021, demonstrating the cytotoxicity of propolis and geopropolis from stingless bee species in different tumor lineages. Confirming the results of the literature review, HF, EAF and HMF inhibited cell proliferation of lung cancer cell lines (H460 and A549) within 48h. The FRGE-9 and FRGE-11 subfractions are three times more active in lung tumor cells (A549) than in normal cells. The bioactive subfractions consist of dihydroxybenzoic acid, apigenin 6- C-glycoside and luteolin-5-O-beta-rutinoside (FRGE-9), diosmetin and myricetin-3- galactoside (FRGE-11). Diosmetin, apigenin-6-C-glucoside, luteolin-5-rutinoside and myricetin-3-galactoside are being identified for the first time in the geopropolis of M. fasciculata. We suggest that the chemical composition of the bioactive subfractions is related to the antitumor action of H460 and A549 lung cancer. The anticancer results found stimulate the continuity of research in the perspective of finding new agents against lung cancer from geopropolis of Melipona fascicula.