Biomedical subjects

D F Horrobin

Publications and source records attributed to D F Horrobin.

454 records · Page 26Linked to original sources

PubMedDate not supplied

Variations in temperature and oxygen content do not alter levels of thiobarbiturate reactive material in human breast tumour cells (ZR-75-1) incubated with gamma-linolenic acid.

The mechanism by which tumour cells may be killed in vitro by exogenous polyunsaturated fatty acids may involve lipid peroxidation. Gamma-linolenic acid caused a dose and time-dependent reduction in ZR-75-1 cell growth. However, altering either the incubator temperature (35, 37 and 39 degrees C) or the oxygen content (16, 21 and 26%) had little effect on either the growth of cells in the presence of gamma-linolenic acid or on thiobarbiturate reactive material levels over a 7 day period. Thus, small changes in cell culture conditions do not affect 18:3n-6 cytotoxicity or markers of lipid peroxidation.

Breast Neoplasms↗

PubMedDate not supplied

Mechanism of lipid peroxidation in cancer cells in response to gamma-linolenic acid (GLA) analyzed by GC-MS(I): Conjugated dienes with peroxyl (or hydroperoxyl) groups and cell-killing effects.

We 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.

Breast Neoplasms↗

PubMedDate not supplied

Metabolism of radiolabelled 18:2n-6 and 18:3n-6 by NIH-3T3 cells and the DT subclone.

The incorporation and metabolism of delta-6-desaturase substrate and product, [1-14C]-linoleic (18:2n-6) and [1-14C]-gamma-linolenic acid (18:3n-6), was examined in NIH-3T3 cells and the DT subclone which differs only in the presence of the v-Ki-ras oncogene. Similar amounts of post delta-6 and delta-5 desaturase metabolites were found in both cell lines indicating that the activity of these important enzymes of fatty acid metabolism was not affected by the expression of the oncogene. However, measurable quantities of the direct elongation product of 18:2n-6, 20:2n-6, were only found in DT cells. Radiolabel was recovered predominantly from the phospholipid fraction at low fatty acid concentrations, whereas neutral lipid labelling occurred when higher concentrations of exogenous fatty acid were present. This effect was most pronounced in DT cells and may result from the presence of the activated ras oncogene.

3T3 Cells↗

PubMedDate not supplied

Expression of catenins in human cancer cells and its regulation by n-6 polyunsaturated fatty acids.

Catenins (alpha, beta, and gamma) are a group of proteins linking E-cadherin with the cytoskeleton. Reduced expression of alpha catenin has been shown in some cancer lines and tissues and is related to the invasive nature of tumour cells. This study examined the effects of n-6 PUFAs on the expression of catenins in a range of human cancer cells by Western blotting. Although most of the cell lines expressed similar levels of beta and gamma catenins, a number of cell lines expressed low levels of alpha catenin. Treatment of cells with gamma linolenic acid (GLA) increased alpha catenin expression in most cell lines, while beta catenin levels were reduced, and gamma catenin expression was unchanged. Linoleic acid and arachidonic acid had not significant effects. We conclude that in human cancer cell lines, the expression of alpha and beta catenins can be regulated by gamma linolenic acid.

Arachidonic Acid↗