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Atividade antiproliferativa e antineoplásica de flavonóides da espécie Brosimum acutifolium em modelo de glioblastoma in vitro
(Universidade Federal do Pará, 2013-05-24) MAUÉS, Luis Antônio Loureiro; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978
Among the tumors that affect the nervous system, glioblastoma multiforme (GBM) is notable by its high degree of aggressiveness and poor prognosis, with an average survival of 15 months from diagnosis. The present study aimed to investigate the antiproliferative and antineoplastic activity of four flavonoids isolated from species Brosimum acutifolium (Huber). two flavans: 4'-hydroxy-7,8-(2",2"-dimethylpyran)-flavan (BAS-1) and 7,4'-dihydroxy-8-(3,3-dimethylallyl)-flavan (BAS-4), and two chalcones: 4,2'-dihydroxy-3',4'-(2",2"-dimetilpirano)-chalcone (BAS-6) and 4,2',4'-trihydroxy-3'-(3,3-dimethylallyl)-chalcone (BAS-7), tested on rat C6 glioblastoma in vitro. Our results showed good cytotoxic activity for flavans (BAS-1, -4) and the chalcone BAS-7, with IC50 less than 100 μM in the MTT viability test, since the chalcone BAS-6, showed no cytotoxicity at the concentrations tested. These flavonoids showed less cytotoxity for non-neoplastic cell (glia), with higher degree of security for the BAS and BAS-4-7, once showed lower cytotoxic effect on non-neoplastic cell, and less hemolytic. Analysis of cell migration showed that treatment with BAS-1; -4 and -7 at low concentrations was effective in promoting the inhibition of cell migration. These three flavonoids were also very promising in inhibiting colony formation and growth, and promote cell cycle arrest with a substantial increase in population SubG0 for treatment with BAS-1 and -4 with 100 μM. The flavans BAS-1 and -4 also showed increased ability to promote losing in the integrity of the mitochondrial membrane potential (ΔΨm) and increased for staining with Annexin V, indicating that these drugs cause death by apoptosis. However the analysis by electron microscopy showed markedly the presence of autophagic vacuoles in the treatment with BAS-4 suggesting that the process of cell death occurs by apoptosis as well as autophagy. Based on these results it can be concluded that the flavonoids BAS-1, -4, and -7 have potential as an anticancer agent in the therapy of GBM and BAS-4 is the most promising of all.