Acrolein cytotoxicity and glutathione depletion in n-3 fatty acid sensitive- and resistant human tumor cells.
Acrolein is a highly reactive unsaturated aldehyde formed endogenously and present in the environment. Acrolein efficiently reduces glutathione-contents and is highly cytotoxic in two lung carcinoma cell lines (A-427 and SK-LU-1) and the glioblastoma cell line A-172. A-427, which has the lowest GSH content of the cell lines, is also more sensitive to growth inhibition and more depleted in GSH after acrolein exposure. A-427 is also highly sensitive to docosahexaenoic acid (22:6 n-3, DHA) and acrolein potentiates the cytotoxic effect of DHA in this cell line, but not in the DHA-resistant cell lines SK-LU-1 and A-172. Surprisingly, the cytotoxic effect of acrolein was partially reversed by vitamin E, selenite and 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen, a Se-glutathione peroxidase mimic) in A-427 cells, but not in SK-LU-1 and A-172 cells. Using the TUNEL assay a strong nuclear fluorescence was observed in DHA-treated A-427 cells, indicating death by apoptosis, whereas acrolein apparently did not induce apoptosis.
Rudra
P K
PK
Institute of Cancer Research and Molecular Biology, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Krokan
H E
HE
D000171:Acrolein / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D011761:Pyrrolidonecarboxylic Acid; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014407:Tumor Cells, Cultured
D013844:Thiazoles; D053778:Thiazolidines; D004281:Docosahexaenoic Acids; D000171:Acrolein; D005979:Glutathione Peroxidase; D005978:Glutathione; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid