Induction of Cell Death of Gastric Cancer Cells by a Modified Compound of the Annonaceous Acetogenin Family

Annonaceous acetogenins are a family of natural products with antitumor activities. The polyether mimic AA005 has been synthesized. The cytotoxic mechanism of AA005 was investigated. It was found that AA005 can induce the cell death of gastric tumor cells. Most AA005-induced cell death is due to necrosis but partial and p53-independent apoptosis is also detected. An expanded study with gastric tumor cells and a cell-free system indicates that AA005 affects NADH:ubiquinone oxidoreductase (complex I; NADH=nicotinamide adenine dinucleotide, reduced form) in the mitochondrial electron transport system. These results show for the first time that the polyether mimic AA005 acts on the same biological target as the natural annonaceous acetogenins.