Effects of natural flavones on membrane properties and citotoxicity of HeLa cells

Abstract

RESUMO: "Efeitos de flavonas naturais em propriedades de membranas e em citotoxicidade de células HeLa". O objetivo deste estudo foi avaliar se eupafolina e hispidulina, flavonas extraídas do Eupatorium littorale Cabrera, Asteraceae, possuíam a capacidade de alterar propriedades das membranas biológicas e promover efeitos citotóxicos. Eupafolina (50-200 µM) reduziu em aproximadamente 30% a velocidade e amplitude do inchamento mitocondrial induzido por valinomicina e 60-100% o inchamento mitocondrial dependente de substrato. Além disso, eupafolina na dose de 200 µM reduziu a transição de permeabilidade mitocondrial em 35% entretanto, a hispidulina não alterou este parâmetro em todas as doses testadas. A avaliação da transição de fase dos lipossomas de DMPC com a sonda DPH demonstrou que ambas as flavonas afetam a fase gel e fluida. Quando lipossomas de membranas mitocondriais e a sonda DPH-PA foram utilizados, houve aumento da polarização de fluorescência promovido pela hispidulina. Eupafolina e hispidulina, na dose de 100 µM, promoveram 40% de redução da viabilidade de células HeLa em 24 h. Nossos resultados sugerem que eupafolina e hispidulina têm efeitos citotóxicos que podem ser explicados em parte pelas alterações promovidas por estas flavonas sobre propriedades de membranas biológicas e sobre a bioenergética mitocondrial.Unitermos: Eupafolina, hispidulina, células HeLa, inchamento mitocondrial. ABSTRACT:The aim of this study was to determine whether eupafolin and hispidulin, flavones extracted from Eupatorium littorale Cabrera, Asteraceae, have the ability to change properties of biological membranes and promote cytotoxic effects. Eupafolin (50-200 µM) decreased approximately 30% the rate and total amplitude of valinomycin induced swelling and 60-100% the energy-dependent mitochondrial swelling. Moreover, eupafolin (200 µM) reduced 35% the mitochondrial permeability transition, and hispidulin did not change this parameter in any of the doses tested. The evaluation of phase transition of DMPC liposomes with the probe DPH demonstrated that hispidulin and eupafolin affect gel and fluid phase. With mitochondrial membrane as model, hispidulin increased the polarization of fluorescence when used DPH-PA probe. Eupafolin and hispidulin (100 µM) promoted a reduction of 40% in cellular viability of HeLa cells in 24 h. Our results suggest that eupafolin and hispidulin have cytotoxic effects that can be explained, in part, by alterations promoted on biological membranes properties and mitochondrial bioenergetics.

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“…Measurement of mitochondrial membrane potential Fluorochrome dye JC-1 was used to evaluate the changes in the mitochondrial membrane potential (MMP) as described previously [31]. Briefly, Huh7 or SMMC7721 cells were incubated with 10 or 20 µM hispidulin for 48 h. Following incubation, the cells were stained with JC-1 for 20 min.…”

Evaluation of the in vitro and in vivo anticancer properties of Moroccan propolis extracts

“…However, the ethanolic extract may act via a direct cytotoxic activity by alteration of biological membranes under the action of natural flavone molecules (Herrerias et al 2010) or by DNA-binding of flavonoid aglycone or flavoloid glycosides compromising DNA duplication and leading to the cell cycle arrest (Wang et al, 2008). It can also act in vivo via a stimulation of multicellular immunity including lymphocyte proliferation (Sà Nunes et al, 2003), natural killer cells and macrophages activation (Dimov et al, 1991;Orsi et al, 2000).…”

Kalanchoe brasiliensisCambess., a Promising Natural Source of Antioxidant and Antibiotic Agents against Multidrug-Resistant Pathogens for the Treatment ofSalmonellaGastroenteritis

“…These compounds can bind to bacterial cell membranes, and some of them can interact with lipids and proteins, altering membrane permeability, and they can also interfere with bacterial quorum sensing [51]. These findings were previously confirmed by Herrerias et al [52] who described the cytotoxic effect of eupafolin that can partially be explained by alterations promoted on biological membrane properties. These reports support the possible mode of action of the detected phenolic compounds, mainly flavonoids, in HEJ70 and HES70.…”