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

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.