Atividade biológica da Biflorina, uma e-naftoquinona isolada das raízes da Capraria biflora L., em células tumorais e não tumorais

Abstract

Biflorin is an o-naphthoquinone with proven cytotoxic effects on tumor cells with antimicrobial, antitumor and antimutagenic activities. Biflorin is an isolated compound taken from the roots of the plant Capraria biflora L. (Schrophulariaceae), indigenous of the West Indies and South America, that inhabits temperate and tropical areas. In the European continent, this plant is used as an ornament. In Brazil, it can be found in the states of Goiás, Minas Gerais and the coastal strip between Piauí in the Northeast, and it extends to the states of Ceará, Pernambuco, Pará and Espírito Santo. In this work, we report the information related to the first structural characterization studies, as well as the latest reports concerning the biological activity of this molecule. It was work verified the cytotoxic effects of biflorin and detection of late apoptosis by in situ analysis. Initially, tumor HeLa and non-tumor HEK-293 cells were treated with biflorin for 24h, 48h and 72h at a range of 5-50 μg/mL. The cytotoxicity was further evaluated exclusively for 48h treatment on six different cell lines Hep-2, HeLa, HT-29, A-375, A-549 and HEK-293. The results indicate that biflorin showed selective cytotoxicity against non-tumor line HEK-293 (IC50 = 56,01 ± 1,17 μg/mL) compared to all tumor cells analyzed in a concentration dependent manner, with IC50 ranging from 29.44 ± 1.32 μg/mL to 47,37 ± 3,21 μg/mL. Substantial morphological changes in HeLa cells were observed after 48h treatment with biflorin with increased concentrations (5- 50 μg/mL) of extract. In addition, in situ immunostaining of annexin V showed that all lines were majority seen at late apoptotic stages in a dose-dependent manner. Late apoptosis for HEK-293 was more evident (77.69 ± 6.68%) at higher extract concentrations compared to all tumor lines tested. The data here presented indicate that biflorin showed an important cytotoxicity against tumor cell lines. However, more studies are needed to better understand the pathways involved in programmed cell death.