In vitro studies on the relationship between polyunsaturated fatty acids and cancer: tumour or tissue specific effects?
In vitro cell culture experiments have lead to the consensus in the literature that certain PUFAs have a selective cytotoxic or anti-proliferative effect on tumour cells and a minimal, or no effect on normal cells. Re-examination of key publications showed that when normal cells were used for comparison, they were generally not from the same cell, tissue, or species type as the tumour cells. Recently, investigations have included more appropriate normal control cells, and though tumour specific cytotoxic/anti-proliferative PUFA effects are found in some cell types, in others the normal cells are more sensitive. Cell type differences were found in the relative ability of individual PUFAs to act. However, within a cell type differences in susceptibility were influenced by grade and stage of tumour, immortalisation and tumourigenic status, cell culture media and cell plating density. Together these results suggest that the consensus is not valid, and that susceptibility to PUFA is cell type specific, and alters during neoplastic progression. Furthermore, the cytotoxic/anti-proliferative effect induced by both n-3 and n-6 PUFAs on a wide variety of cell types, associated with an increase in lipid peroxidation in vitro, cannot account for the in vivo data on the relationship between dietary fat and certain cancers. However, the effects of PUFAs and their metabolites on cell signalling pathways may explain the in vivo data.
Diggle
Christine P
CP
ICRF Cancer Medicine Research Unit, St James's University Hospital, Leeds LS9 7TF, UK. medcpd@cancermed.leeds.ac.uk
D000818:Animals; D016022:Case-Control Studies; D016923:Cell Death; D002455:Cell Division; D004032:Diet; D064429:Fatty Acid Synthases / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D005231:Fatty Acids, Unsaturated; D064429:Fatty Acid Synthases