gamma-linolenic-acid and Neoplasm-Metastasis

Large scale human epidemiological studies indicate that high intakes of linoleic acid protect against the development of cancer. One mechanism may be the generation of 13-HODE from linoleic acid. 13-HODE prevents cell adhesion to endothelial cells and can inhibit cancer metastasis. 13-HODE synthesis is enhanced by cyclic AMP. Gamma-linolenic acid, a desaturated metabolite of linoleic acid, causes substantial stimulation of 13-HODE synthesis. A fall in gamma-linolenic acid synthesis with age may be related to the age-related fall in 13-HODE formation.

Topics: Animals; Anticarcinogenic Agents; Cell Adhesion; Cyclic AMP; Endothelium, Vascular; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids; Neoplasm Metastasis

Gamma linolenic acid (GLA) has been proposed as a valuable new cancer therapy having selective anti-tumour properties with negligible systemic toxicity. Proposed mechanisms of action include modulation of steroid hormone receptors. We have investigated the effects of GLA with primary hormone therapy in an endocrine-sensitive cancer. Thirty-eight breast cancer patients (20 elderly Stage I-II, 14 locally advanced, 4 metastatic) took 8 capsules of oral GLA/day (total = 2.8 g) in addition to tamoxifen 20 mg od (T+GLA). Quality and duration of response were compared with matched controls receiving tamoxifen 20 mg od alone (n = 47). Serial tumour biopsies were taken to assess changes in oestrogen receptor (ER) and bcl-2 expression during treatment. GLA was well tolerated with no major side effects. T+GLA cases achieved a significantly faster clinical response (objective response vs. static disease) than tamoxifen controls, evident by 6 weeks on treatment (p = 0.010). There was significant reduction in ER expression in both treatment arms with T+GLA objective responders sustaining greater ER fall than tamoxifen counterparts (6-week biopsy p = 0.026; 6-month biopsy p = 0.019). We propose GLA as a useful adjunct to primary tamoxifen in endocrine-sensitive breast cancer. The effects of GLA on ER function and the apparent enhancement of tamoxifen-induced ER down-regulation by GLA require further investigation.

Topics: Administration, Oral; Aged; Antineoplastic Agents, Hormonal; Biopsy; Breast Neoplasms; Disease-Free Survival; Female; gamma-Linolenic Acid; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Proto-Oncogene Proteins c-bcl-2; Receptors, Estrogen; Tamoxifen

Topics: Aged; Antineoplastic Agents; Clinical Trials as Topic; Colonic Neoplasms; gamma-Linolenic Acid; Humans; Linolenic Acids; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Random Allocation; Rectal Neoplasms

The early detection of colorectal cancer and determination of its metastatic potential are important factors to set up more efficacious therapeutic strategies. In the present study, we hypothesize that fatty acids analysis in colorectal cancer patients can discriminate between metastatic and non-metastatic patients. Fifty-one consecutive patients with histologically proven colorectal cancer were enrolled in the study and the presence of synchronous metastasis was detected in 25 of these 51 patients. Fatty acid profile analysis in red blood cell membranes was not able to discriminate the metastatic colorectal cancer patients from those without metastasis. However, significant differences in the tumor tissue fatty acid profile were found in metastatic cancer patients when compared to patients without metastasis. Metastatic patients showed significantly lower percentages of Eicosapentaenoic acid (EPA) and higher levels of γ-linolenic acid (GLA), a

Topics: Colorectal Neoplasms; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Fatty Acids, Omega-6; gamma-Linolenic Acid; Humans; Neoplasm Metastasis

Inhibition of angiogenesis shows considerable promise as a strategy for treating solid malignancies. Induction of collagenase by protein kinase C plays an important role in the angiogenic process as well as in metastasis. Lipoxygenase products are required for endothelial cell mitosis, and also promote collagenase production. By down-regulating hormonal activation of protein kinase C and modulating eicosanoid metabolism, ingestion of omega-3-rich fish oils may impede angiogenesis and reduce tumor invasiveness-thus rationalizing the growth-retardant and anti-metastatic effects of fish oil feeding almost invariably seen in animal tumour models. Certain other anti-inflammatory agents-including cromolyn (an inhibitor of protein kinase C activation) and gamma-linolenic acid (which indirectly inhibits lipoxygenase) may have analogous tumour-retardant activity. Clinical application of supplemental fish oil in cancer therapy is long overdue.

Topics: Animals; Down-Regulation; Eicosanoids; Fish Oils; gamma-Linolenic Acid; Humans; Lipoxygenase Inhibitors; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Neovascularization, Pathologic; Protein Kinase C

This hypothesis proposes that the essential fatty acids (EFAs), linoleic acid (LA) and gamma-linolenic acid (GLA), play important roles in cancer treatment. Oxidation of LA by lipoxidase especially increases tumour cell death, whilst GLA inhibits urokinase-type plasminogen activator (uPA) activity. Increased uPA activity is: firstly, responsible for cancer invasion and metastasis and secondly, responsible for proteolysis of lipoxidase which favours a decrease in cancer cell death. Addition of LA and GLA to available therapeutic regimens may be worth considering in cancer treatment.

Topics: Antineoplastic Agents, Phytogenic; Cell Death; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids; Lipoxygenase; Models, Biological; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Oxidation-Reduction; Plant Oils; Urokinase-Type Plasminogen Activator

The effectiveness of dietary n-3 plant and marine fatty acids and n-6 gamma-linolenic acid (GLA) was tested as an antimetastatic modality in the experimental model of metastasis of 13762MAT:B mammary adenocarcinoma cells. Weanling female Fischer 344 rats were placed on one of the following diets: 1-23.52% blackcurrant oil (BCO), II-23.52% corn oil (CO), III-15.52% BCO + 8% fish oil (FO), IV-20.52% FO + 3% CO, and V-5% CO. After 8 weeks, 15 rats per group were injected i.v. with 10(5) cells and diets were continued until sacrifice. In the 23.52% CO group (II), the number of small (< 2 mm) and large (> 2 mm) lung metastatic foci and their total volume were significantly greater than the BCO- and/or FO-fed groups (I, II and IV). Although the number of small metastatic foci was comparable in the 5% and 23.52% CO groups, the number of large foci and the total tumor volume were reduced in the 5% CO group. These results suggest that, compared to a low-corn oil diet or a high-fat diet containing a mixture of marine and plant n-3 fatty acids plus n-6 GLA, a 23.52% corn oil diet can enhance experimental metastasis of mammary adenocarcinoma cells. Total number of metastatic foci and tumor volume were the smallest in group III, receiving a combination of plant and marine n-3 fatty acids.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Body Weight; Fatty Acids, Omega-3; Female; Fish Oils; gamma-Linolenic Acid; Linolenic Acids; Lung Neoplasms; Mammary Neoplasms, Experimental; Neoplasm Metastasis; Phospholipids; Plant Oils; Rats; Rats, Inbred F344; Survival Analysis