RESUMEN
Curative properties of some medicinal plants such as the Feijoa sellowiana Bert. (Myrtaceae), have been often claimed, although the corresponding molecular mechanism(s) remain elusive. We report here that the Feijoa acetonic extract exerts anti-cancer activities on solid and hematological cancer cells. Feijoa extract did not show toxic effects on normal myeloid progenitors thus displaying a tumor-selective activity. In the Feijoa acetonic extract, fractionation and subsequent purification and analyses identified Flavone as the active component. Flavone induces apoptosis which is accompanied by caspase activation and p16, p21 and TRAIL over-expression in human myeloid leukemia cells. Use of ex vivo myeloid leukemia patients blasts confirms that both the full acetonic Feijoa extract and its derived Flavone are able to induce apoptosis. In both cell lines and myeloid leukemia patients blasts the apoptotic activity of Feijoa extract and Flavone is accompanied by increase of histone and non-histone acetylation levels and by HDAC inhibition. Our findings show for the first time that the Feijoa apoptotic active principle is the Flavone and that this activity correlates with the induction of HDAC inhibition, supporting the hypothesis of its epigenetic pro-apoptotic regulation in cancer systems.
Asunto(s)
Feijoa/química , Flavonoides/farmacología , Flavonoides/uso terapéutico , Inhibidores de Histona Desacetilasas , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Flavonas , Células HeLa , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Modelos Biológicos , Neoplasias/patología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Células Tumorales Cultivadas , Células U937RESUMEN
Dried mosses (five moss species) were progressively extracted and subjected to a four-step Craig distribution. Seven pure flavonoids were isolated and identified. The flavonoids were the flavones apigenin, apigenin-7-O-triglycoside, lucenin-2, luteolin-7-O-neohesperidoside, saponarine and vitexin; and the biflavonoid bartramiaflavone and they were submitted to biological tests. The tests were performed in vitro on spore germination and protonemal growth of the moss Tortula muralis and on seed germination and root growth of Raphanus sativus. Flavonoids caused a decrease in the percentage of spore germination, protonemal development and root growth. In addition they caused morphological alterations, such as forked tips, swollen apices, rounded cells and early formation of brood cells in the protonemata. Data were discussed in relation to the presence of allelochemicals in mosses.