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Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 02/06 Podcast
Identification of novel mechanisms of action contributing to the biological activity of cytotoxic natural compounds

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

Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 02/06 vor 20 Jahren

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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.