RESUMEN
Metaxya rostrata C. Presl (Metaxyaceae) is a common tree fern in Central and South America that is used for the treatment of intestinal ulcers and tumours in ethnic medicine. Using a bioactivity-guided strategy 2-deprenyl-rheediaxanthone B (XB) has been isolated as one of the active principles in this plant. XB induced loss of cell viability in colorectal cancer cell lines at IC50 concentrations of 11-23 µM. This was caused by both accumulation of cells in the G2- and S-phase as well as by induction of active cell death in a time and concentration-dependent manner. Cells exposed to XB were incapable of undergoing regular mitosis due to down-regulation of FoxM1 and absence of chromosome condensation. The apoptosis-related proteins Bcl2 and Bclxl were up-regulated so that Caspase 3 was not activated and classical apoptosis was not observed. However, XB triggered damage pathways down-stream of ATR and activated Caspase 2 causing cell death by a mechanism similar to mitotic catastrophe. Our observations are the first to show the cytotoxic activity of 2-deprenyl-rheediaxanthone B and indicate that XB is an interesting new lead compound for cancer therapy that merits further development.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Helechos/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Células CACO-2 , Caspasa 2/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Células HCT116 , Humanos , Concentración 50 Inhibidora , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
Two new natural compounds, (1R,2E)-2-(6-hydroxyhexylidene)cyclopropyl-ß-D-glucopyranoside (1) and (6E)-6-[(2R)-2-(ß-D-glucopyranosyloxy)cyclopropylidene]hexanoic acid (2), glucosides of a very rare methylidenecyclopropane alcohol, as well as two known glycosides of phenolic acids, namely 4-O-ß-D-glucopyranosylcaffeic acid (3) and (E)-4-O-ß-D-glucopyranosylcoumaric acid (4), and methyl α-fructofuranoside (5) were isolated for the first time from the rhizomes of the tree fern Metaxya rostrata C.Presl. The structures were elucidated on the basis of detailed spectroscopic data analysis, and the structure of 1 was additionally confirmed by X-ray crystal-structure analysis.