2-Deprenyl-Rheediaxanthone B Isolated from Metaxya rostrata Induces Active Cell Death in Colorectal Tumor Cells

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Abstract

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 IC 50 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 Bcl 2 and Bcl xl 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. © 2013 Kainz et al.

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Kainz, K. P., Krenn, L., Erdem, Z., Kaehlig, H., Zehl, M., Bursch, W., … Marian, B. (2013). 2-Deprenyl-Rheediaxanthone B Isolated from Metaxya rostrata Induces Active Cell Death in Colorectal Tumor Cells. PLoS ONE, 8(6). https://doi.org/10.1371/journal.pone.0065745

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