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

Abstract

Summary Sterculic acid, a A-9-desaturase inhibitor, administered to rats caused a rise in the stearic:oleic acid ratio of total lipids in peripheral red cells, serum and liver (P <0.001). As a reduction in the stearic:oleic acid ratio has been described in cancer cells, we investigated the effect of sterculic acid on tumour growth. Female F344 rats were injected subcutaneously with two different doses of sterculic acid for 4 weeks prior to, and 4 weeks following, implantation of a nitrosomethylurea-induced mammary tumour. Tumour growth was inhibited equally by the two doses of sterculic acid (P <0.001). 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. The desaturation of stearic to oleic acid is mediated by A-9-desaturase an important enzyme in the control of tissue fatty acid desaturation. Inhibition of this enzyme, therefore, may inhibit cancer cell growth. Sterculic acid is the most potent A-9-desaturase inhibitor known and is itself a naturally occurring cyclopropene fatty acid derived from a number of plant sources such as Sterculia foetida seed oil. It inhibits the A-9-desaturate system, and de novo synthesis of saturated fatty acids and cholesterol, is unaffected (Zoeller & Wood, 1985).The aims of this study were to assess the tolerability of injected sterculic acid in rats and its effect on tissue fatty acid composition and to relate tissue fatty acid composition to inhibition of the growth of a transplanted mammary tumour in rats. Materials and methods AnimalsFischer F344 rats were obtained from Harlan Olac Ltd (Bicester, UK) and were maintained in a 12-hour light/dark cycle. They were fed a standard diet (CRM; Biosure Ltd, Cambridge, UK) and water ad libitum. Male rats aged 4-6 weeks were used to investigate the effects of sterculic acid on body fat composition, and for the other experiments, female rats aged 4-6 weeks were used.Sterculic acid Sterculic acid (98% pure) was obtained from Reading Scientific Ltd (Reading, England). It was blown with nitrogen and stored in sealed containers at -20°C. It was dissolved in liquid paraffin to a volume of 0.5 ml before administration by subcutaneous injection.The effect of sterculic acid on body fat acids The rats were randomised to a treated group which received sterculic acid (0.125 ml (90 mg) diluted 1:4 with liquid paraffin) by subcutaneous injection three times a week and an untreated control group. Blood for fatty acid analysis was taken from the lateral tail vein under anaesthetic at fortnightly intervals. Thirteen animals completed the experiment in the treated group...

Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas

“…Several treatments or conditions that are associated with hepatocarcinogenesis (57, 59) also increase SCD1 expression, and SCD1 levels are higher in rat mammary carcinomas (60) and in mice that are genetically susceptible to hepatocarcinogenesis (61). Sterculic acid, an inhibitor of SCD1 activity, blocks rat mammary carcinogenesis (62). In our study, the increased SREBP1c expression observed in AlbCrePten flox/flox mice may have induced SCD1 upregulation and an accumulation of monounsaturated fatty acids that may have promoted hepatocarcinogenesis.…”

Stearoyl-CoA Desaturase Is Involved in the Control of Proliferation,Anchorage-independent Growth, and Survival in Human TransformedCells

“…In addition, the proportional enrichment of phospholipids with SFA promotes cytostatic effects in cancer cells (39). Furthermore, sterculic acid, an inhibitor of SCD activity, exhibits an anti-proliferative action in neoplastic cells likely by increasing the relative abundance of SFAs (40). Finally, the inhibition of fatty acid synthesis observed in SCDdepleted cells may be also responsible for the decrease in cell proliferation.…”

Enzymatic production of sterculic acid from the novel Phoenix tree seed oil: Optimization and kinetic study

“…Sterculic acid also can inhibit mammary carcinoma growth in rats (Khoo et al, 1991). In our previous work (Sun and Li, 2016), we found that Phoenix tree seed oil is rich in sterculic acid (S, 23.2%).…”