Acrolein cytotoxicity and glutathione depletion in n-3 fatty acid sensitive- and resistant human tumor cells

Acrolein is a highly reactive unsaturated aldehyde formed endogenousl y and present in the environment. Acrolein efficiently reduces glutat hione-contents and is highly cytotoxic in two lung carcinoma cell lin es (A-427 and SK-LU-1) and the glioblastoma cell line A-172. A-427, w hich has the lowest GSH content of the cell lines, is also more sensi tive to growth inhibition and more depleted in GSH after acrolein exp osure. 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 revers ed 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 f luorescence was observed in DHA-treated A-427 cells, indicating death by apoptosis, whereas acrolein apparently did not induce apoptosis.