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.
Huang
Guo-Rui
GR
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, China.
Jiang
Sheng
S
Wu
Yu-Lin
YL
Jin
Yan
Y
Yao
Zhu-Jun
ZJ
Wu
Jia-Rui
JR
D029061:Annonaceae / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009154:Mutation; D013274:Stomach Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C483824:AA005; D000972:Antineoplastic Agents, Phytogenic; D005233:Fatty Alcohols; D007783:Lactones; D016159:Tumor Suppressor Protein p53