Stearic acid and carcinogenesis

Abstract

Summary Decreased membrane rigidity is one of the characteristics of malignant cells, resulting in part from the desaturation of stearic acid into oleic acid. In this study we investigated the influence of stearic acid on tumour cell inhibition in vitro and tumour development in vivo. Stearic acid inhibited the colony-forming ability of 4 out of 5 rat and two human tumour continuous cell lines in vitro. In contrast, the colony-forming ability of rat fibroblasts was not inhibited and that of human foetal lung fibroblasts was inhibited at a higher dose than that required to inhibit human tumour cell lines. Using a model of rat mammary carcinoma induced by nitroso-methyl urea (NMU) the subcutaneous injection of stearic acid at weekly intervals prevented tumour development in 5 to 10 rats. Using iodostearic acid twice weekly, 11 of 19 rats were alive and tumour free at week 22 whilst all of 14 animals injected with NMU alone had died of tumour by the 16th week. The ratio of stearic to oleic acids in erythrocyte membranes was significantly reduced in the tumourbearing rats, but was normal in tumour-free animals treated with stearic or iodostearic acid. These preliminary data indicate that stearic acid inhibits tumour development in rats.The regulation of membrane rigidity is essential for homeostasis (Cooper, 1977) and the metabolic rates of many essential cell enzymes depend on it (Sandemann, 1979). In general, decreased membrane rigidity leads to increased cell metabolism and also higher division rates, features characteristic of the malignant cell. Corvin et al. (1977) have also shown that alteration of membrane lipid structure may change the cancer cell phenotype. The evidence for decreased membrane rigidity in malignant cells is derived from direct physical measurements and lipid analysis. Using fluorescent probes and magnetic resonance studies, decreased microviscosity (decreased membrane rigidity) was found in plasma membranes, as well as in isolated lipid vesicles from leukaemic cells (Petitou et al., 1978;Mountford et al., 1986). Fatty acid analysis of lipids extracted from transformed cells, cell lines, leukaemic cells and solid tumour tissue showed a consistent increase in the oleic acid content relative to stearic acid Wood et al., 1985).The normal metabolic flow results in conversion of the saturated stearic acid to the monounsaturated oleic acid by the enzyme complex delta 9 desaturase. The ratio of stearic to oleic acid, the so-called saturation index (SI), reflects the activity of this enzyme . A significant decrease in the SI of red blood cell membranes was noted in a range of human and animal malignancies (Habib et al., 1987b), and it was suggested that this index could be used as a tumour marker. It has also been reported that there is a decrease in the SI of red blood cell membranes in patients suffering from the Acquired Immune Deficiency Syndrome .We have noted previously that interferon inhibits the desaturation of stearic acid in vitro (Apostolov & Barker, 1981) and that interferon treatment...

Biomarkers of dietary fatty acid intake and the risk of breast cancer: A meta‐analysis

“…Stearic acid has already been found to act directly by inhibiting the proliferation of human tumors cells in vitro. 39,40 Most oleic acid in human body is derived from the saturated stearic acid by desaturation of this latter by the enzyme delta 9 desaturase (⌬9-d). Overexpression of this enzyme and consequently high levels of oleic acid has been shown to be required for tumor development in experimental animal studies.…”

Manipulation of body fat composition with sterculic acid can inhibit mammary carcinomas in vivo

“…When compared with a control diet, a diet containing 14% stearic acid reduced the yield and prolonged the latency of spontaneously developing mammary carcinomas in strain A/ St mice (Bennett, 1984). Both injected stearic acid and an iodinated analogue, iodostearic acid, were also shown to inhibit nitrosomethylurea-induced mammary carcinogenesis in rats, and using in vitro clonogenic assay malignant cells were selectively inhibited (Habib et al, 1987). Stearic acid inhibited the growth of mouse LM cells in vitro (Doi et al, 1978), and the growth of neoplastic rat mammary epithelial cells was inhibited by stearic acid whereas monounsaturated fatty acids such as oleic acid and polyunsaturated fatty acids promoted growth in vitro (Wicha et al, 1979).…”

“…When individual fatty acids were investigated, linoleate and oleate increased the growth of nitrosomethylureainduced mammary tumour in vivo (Chan et al, 1983). By contrast, stearic acid inhibited mammary tumour cells in vitro (Doi et al, 1978;Wicha et al, 1979) and also in vivo (Bennett, 1984;Habib et al, 1987). Stearic acid may inhibit cancer cell growth by increasing the cellular stearic:oleic acid ratio and hence the balance of saturated and unsaturated fatty acids in the tissues.…”

“…A rise in the stearic:oleic acid ratio of tumours was observed in rats treated for only 16 (Segi et al, 1966;Drasar & Irving, 1973). Monounsaturated, saturated and polyunsaturated fats were found to correlate with breast cancer incidence in a case control study (Miller et al, 1978 al., 1978;Wicha et al, 1979) and also in vivo (Bennett, 1984;Habib et al, 1987). Stearic acid may inhibit cancer cell growth by increasing the cellular stearic:oleic acid ratio and hence the balance of saturated and unsaturated fatty acids in the tissues.…”

Optimizing Dietary Fat to Reduce Breast Cancer Risk: Are we there Yet?

“…Similarly, a 17% stearate diet/ 3% safflower oil diet was shown to decrease tumor size in animals injected with MDA-MB-435 cells into the mammary fat pad [46]. When Habib et al injected stearate into NMU treated animals, they observed a decreased number of tumors, decreased latency period until first tumor development, and decreased tumor size [47]. These studies indicate that in addition to dietary modification, it may be possible to alter fatty acid concentrations in patient through injections of individual fatty acids.…”