Key role of mitochondria in cerulenin-mediated apoptosis.

Article Details

Citation

Copy to clipboard

Heiligtag SJ, Bredehorst R, David KA

Key role of mitochondria in cerulenin-mediated apoptosis.

Cell Death Differ. 2002 Sep;9(9):1017-25.

PubMed ID

12181752 [ View in PubMed

]

Abstract

Cerulenin, a fungal metabolite, is known to be a specific inhibitor of fatty acid synthase. Here we report that cerulenin is an effective inducer of apoptosis in different wild-type p53 and mutant p53 tumor cell lines, whereas normal human keratinocytes and fibroblasts are resistant to the apoptotic effect. To get more insight into the mechanisms of how cerulenin induces apoptosis we investigated several signal transduction molecules, including p53, p73, p21/WAF1, Bax, cytochrome c, and caspases 3 and 9. Our data strongly indicate that mitochondria play a key role in the cerulenin-mediated pathway. Bax overexpression correlated with the extent of apoptosis and appears to be regulated in a p53-independent manner. The significance of the mitochondrial pathway for the cerulenin-mediated apoptosis was confirmed by the rapid mitochondrial release of cytochrome c both in wild-type p53 and mutant cell lines. Interestingly, the rapid release of cytochrome c was not accompanied by a breakdown of the mitochondrial potential. Instead, the complete disruption of the mitochondrial function coincided with the appearance of a p18 kDa cleavage product of Bax.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cerulenin	Fatty acid synthase	Protein	Humans	Yes	Inhibitor	Details