title: Prenylated flavanone derivatives isolated from Erythrina addisoniae are potent inducers of apoptotic cell death.
abstract: Extracts of Erythrina addisoniae are frequently used in the traditional medicine of Western Africa, but insufficient information about active compounds is available. From the stem bark of E. addisoniae, three (1, 2, 4) and three known (3, 5, 6) flavanones were isolated: addisoniaflavanones I and II, containing either a 2″,3″-epoxyprenyl moiety (1) or a 2″,3″-dihydroxyprenyl moiety (2) were shown to be highly toxic (MTT assay: EC50 values of 5.25±0.7 and 8.5±1.3 μM, respectively) to H4IIE hepatoma cells. The cytotoxic potential of the other isolated flavanones was weaker (range of EC50 values between 15 and >100 μM). Toxic effects of addisoniaflavanone I and II were detectable after 3h (MTT assay). Both compounds induced an apoptotic cell death (caspase-3/7 activation, nuclear fragmentation) in the hepatoma cells and, at high concentrations, also necrosis (membrane disruption: ethidium bromide staining). Formation of DNA strand breaks was not detectable after incubation with these compounds (comet assay). In conclusion, the prenylated flavanones addisoniaflavanones I and II may be of interest for pharmacological purposes due to their high cytotoxic and pro-apoptotic potential against hepatoma cells.
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-University, Universitätsstraße 1, 40225 Düsseldorf, Germany.
authors.forename: Claus M
authors.initials: CM
authors.lastname: Passreiter
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-University, Universitätsstraße 1, 40225 Düsseldorf, Germany.
authors.forename: Anke-Katrin
authors.initials: AK
authors.lastname: Suckow-Schnitker
authors.affiliation: Institute of Toxicology, Heinrich-Heine-University, P.O. Box 101007, 40001 Düsseldorf, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kulawik
authors.affiliation: Bradford School of Pharmacy, University of Bradford, Richmond Road, West Yorkshire BD 7 1 DP, UK.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Addae-Kyereme
authors.affiliation: Bradford School of Pharmacy, University of Bradford, Richmond Road, West Yorkshire BD 7 1 DP, UK.
authors.forename: Colin W
authors.initials: CW
authors.lastname: Wright
authors.affiliation: Institute of Toxicology, Heinrich-Heine-University, P.O. Box 101007, 40001 Düsseldorf, Germany; Institute of Agricultural and Nutritional Sciences, Biofunctionality of Secondary Plant Compounds, Martin Luther University Halle-Wittenberg, Weinbergweg 22 (Biozentrum), 06120 Halle/Saale, Germany. Electronic address: wim.waetjen@landw.uni-halle.de.
authors.forename: Wim
authors.initials: W
authors.lastname: Wätjen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004895:Erythrina / Q000737:chemistry*; D044950:Flavanones / Q000737:chemistry* / Q000494:pharmacology*; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D016488:Medicine, African Traditional; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D054876:Prenylation; D051381:Rats
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D007529:Isoflavones; C000608322:addisoniaflavanone I; C000608323:addisoniaflavanone II; D053148:Caspase 3
keywords: Apoptosis; Bioactivity; Cytotoxicity; Flavonoid; Prenylation