AbstractWe have investigated the nature of lipid peroxidation occurring in association with cancer-killing produced by gamma-linolenic acid (GLA) and iron (Fe) in cultured human breast cancer cells (ZR-75-1: ZR). UV-spectrophotometry, high performance liquid chromatography (HPLC) and gas chromatography (GC) or gas chromatography-mass spectrometry (GC-MS) have been used to analyze lipid peroxides and their derivatives. Formation of conjugated dienes (CD), the conversion of triphenylphosphine (TPP) to its oxide (TPPO), and the simultaneous production of hydroxy polyunsaturated fatty acids (PUFA-OHs) from these corresponding PUFAs hydroperoxides (PUFA- OOHs) were analyzed in the total lipid extract of ZR cells and of normal human skin fibroblasts (CCD-41Sk:Sk). Fe enhanced the formation of both the CD and TPPO and increased the percentage of dead cells, while vitamin E inhibited these effects. Neither of these events was observed at any significant level in Sk cells. Identity of PUFA-OHs was confirmed by determining the regional positions of the hydroxyl group by GC-MS analysis of hydrogenated methyl ester tert-butyldimethylsilyl ether alcohol derivatives (Me-H2-PUFA-O-TBDMS). The regional isomers identified were 15-, 12- and 8-OH 20 carbon and 13-OH 18 carbon fatty acid derivatives. These results suggest that the increased formation of conjugated dienes and/or hydroperoxyl (or peroxyl) groups in PUFA molecules is relevant to the cancer cell-killing effect of GLA+Fe.
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