Efeitos antioxidantes e anticâncer de geoprópolis de abelhas sem ferrão do cerrado brasileiro

Abstract

Used for millennia, natural products have been essential in the treatment of numerous diseases and are considered an invaluable source of bioactive substances with pharmacological properties. Among these substances, those with antioxidant action stand out, capable of preventing diseases associated with oxidative stress, including cancer. In addition to prevention, natural products are investigated for their antineoplastic potential, with the aim of developing more efficient drugs and/or with reduced adverse effects. In this context, the objective of this study was to investigate the effect of hydroethanolic extracts of geopropolis produced by the stingless bees Melipona orbignyi (EGMO) and Melipona quadrifasciata anthidioides (EGMQ) against oxidative damage in vitro and in vivo and to evaluate their effect on different cancer cell lines. The effect against oxidative damage in vitro was evaluated in proteins and DNA. To investigate the in vivo effects on oxidative and thermal stress and longevity, the Caenorhabditis elegans model was used. The effects of EGMO and EGMO were investigated in rhabdomyosarcoma, lung carcinoma, melanoma and leukemia cells using the MTT cell viability assay. The inhibition of cell migration of melanoma cell lines was evaluated by the scratch assay. The mechanisms of death were investigated using flow cytometry and through the use of pharmacological inhibitors. The results show that EGMO and EGMQ promoted the reduction of protein oxidation and DNA fragmentation. The extracts were non-toxic in the in vivo model and promoted protection against juglone-induced oxidative stress and against heat stress in C. elegans. Furthermore, EGMO and EGMQ increased the life expectancy of nematodes in a dose-dependent manner. Regarding the anticancer effect, both extracts promoted selective cytotoxicity in all cancer cell lines evaluated. EGMO and EGMQ also promoted an inhibitory effect on cell migration of all melanoma cell lines. The cytotoxicity promoted by EGMO/EGMQ in B16F10-Nex2 murine melanoma and Jurkat leukemia cells was induced predominantly via caspase-dependent apoptosis and then by necroptosis through RIPK-1 activation. In K562 cells, geopropolis extracts promoted cytotoxic action via induction of caspase-dependent apoptosis. Together, these results demonstrate that geopropolis extracts from M. orbignyi and M.q. anthidioides have biological properties with potential therapeutic application in the prevention and treatment of diseases triggered by oxidative stress and/or cancer cell proliferation.