title: 2-deprenyl-rheediaxanthone B isolated from Metaxya rostrata induces active cell death in colorectal tumor cells.
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 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.
authors.affiliation: Medical University Vienna, Department of Medicine 1, Institute of Cancer Research, Vienna, Austria.
authors.forename: Kerstin P
authors.initials: KP
authors.lastname: Kainz
authors.forename: Liselotte
authors.initials: L
authors.lastname: Krenn
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Erdem
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Kaehlig
authors.forename: Martin
authors.initials: M
authors.lastname: Zehl
authors.forename: Wilfried
authors.initials: W
authors.lastname: Bursch
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Marian
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018938:Caco-2 Cells; D053143:Caspase 2 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism; D029624:Ferns / Q000737:chemistry*; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D053143:Caspase 2