Identification of novel mechanisms of action contributing to the biological activity of cytotoxic natural compounds

López Antón, Nancy (2006): Identification of novel mechanisms of action contributing to the biological activity of cytotoxic natural compounds. Dissertation, LMU München: Fakultät für Chemie und Pharmazie

Abstract

Part I: Cephalostatin 1 is a potent marine cytotoxic compound reported to induce apoptosis without cytochrome c release and apoptosome formation. This work shows that, however, caspase-9 is essential for the induction of apoptosis. Cephalostatin 1 induces endoplasmic reticulum stress together with the activation of the ASK1/JNK cascade as well as caspase-4 and caspase-2, which act upstream of caspase-9 and are required for apoptosis. Part II: Sesquiterpene lactones are secondary plant metabolites with cytotoxic and anti-inflammatory activities. It was found that 11α,13-dihydrohelenalin acetate (α,β-unsaturated cyclopentenone) induces classical apoptosis whereas 7-hydroxycostunolide (α-methylene-γ-lactone) induces a novel form of cell death characterised by a fast and strong exposure of phosphatidylserine in agreement with a strong activation of phagocytosis in cocultured macrophages.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: cephalostatin, apoptosis, caspase-4, caspase-9, sesquiterpene lactones, macrophage, phagocytosis
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 540 Chemie
• Fakultäten: Fakultät für Chemie und Pharmazie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 3. April 2006
• 1. Bericht­erstatter:in: Vollmar, Angelika