Effects Of Gamma-linolenic Acid Research Articles

Mitochondrial apoptosis and curtailment of hypoxia-inducible factor-1α/fatty acid synthase: A dual edge perspective of gamma linolenic acid in ER+ mammary gland cancer.

Gamma linolenic acid is a polyunsaturated fatty acid having selective anti-tumour properties with negligible systemic toxicity. In the present study, the anti-cancer potential of gamma linolenic acid and its effects on mitochondrial as well as hypoxia-associated marker was evaluated. The effect of gamma linolenic acid was scrutinised against ER + MCF-7 cells by using fluorescence microscopy, JC-1 staining, dot plot assay and cell cycle analysis. The in vitro results were also confirmed using carcinogen (n-methyl-n-nitrosourea) induced in vivo model. The early and late apoptotic signals in the conjugation with mitochondrial depolarisation were found once scrutinised through mitochondrial membrane potential and life death staining after gamma linolenic acid treatment. Gamma linolenic acid arrested the cell cycle in G0/G1 phase with the majority of cell populations in the early apoptotic stage. The translocation of phosphatidylserine was studied through annexin-V FITC dot plot assay. The markers of cellular proliferation (decreased alveolar bud count, histopathological architecture restoration and loss of tumour micro-vessels) were diminished after gamma linolenic acid treatment. Gamma linolenic acid ameliorates the biological effects of n-methyl-n-nitrosourea persuading the mitochondrial mediated death pathway and impeding the hypoxic microenvironment to make a halt in palmitic acid synthesis. SIGNIFICANCE: The present study elaborates the effect of gamma linolenic acid on mammary gland cancer by following mitochondrial-mediated death apoptosis pathway. Gamma linolenic acid also inhibits cell-wall synthesis by the curtailment of HIF-1α and FASN level in mammary gland cancer.

Gamma-linolenic and pinolenic acids exert anti-inflammatory effects in cultured human endothelial cells through their elongation products

AbstractIt is recommended that humans consume fatty fish twice a week to increase dietary intake of eicosapentaenoic acid (EPA) and docosapentaenoic acid (DHA) to achieve long-term health benefits. However current stocks of fish are likely insufficient to meet the needs of humans. Plant-derived polyunsaturated fatty acids (PUFAs) gamma-linolenic acid (GLA) and pinolenic acid (PIN) may provide sustainable land-based sources of bioactive fatty acids.Anti-inflammatory effects of GLA and PIN were compared to EPA and DHA in cultured EA.hy926 cells. Cells were treated with PUFAs (10, 25 and 50 μM) for 48 hours prior to stimulation with tumour necrosis factor for 24 hours. Incorporation of PUFA was measured by gas chromatography; inflammatory responses were measured by ELISA and flow cytometry.All fatty acids were incorporated into EA.hy926 cells, after 48 hours, in a dose dependent manner (10 and 50 μM). Pre-treatment with GLA and PIN (50 μM) resulted in significant increases in their elongation products, dihomo-γ-linolenic acid (DGLA) (p < 0.0001) from GLA and eicosatrienoic (ETrA) (p < 0.0001) from PIN.Pre-treatment with GLA, PIN, EPA or DHA (50 μM) had differential effects depending on fatty acid and cytokine examined. Pre-treatment of EA.hy926 cells with both GLA and PIN resulted in a lower concentration of soluble ICAM-1 (p < 0.01); however EPA and DHA showed greater reduction (p < 0.0001). MCP-1 production was significantly lower after treatment with PIN (p < 0.05), again to a lesser extent than EPA and DHA (p < 0.0001). Pre-treatment with EPA and DHA (50 μM) resulted in lower cell surface expression of ICAM-1 (p < 0.001, p < 0.0001), an effect not observed with GLA or PIN.Anti-inflammatory effects of GLA and PIN were possibly due to their elongation products, and therefore silencing of elongase 5 (ELOVL5) was explored. ELOVL5 siRNA significantly inhibited the production of DGLA and ETrA in EA.hy926 cells pre-treated with GLA and PIN (50 μM). Furthermore significant decreases in sICAM-1 and MCP-1 were not seen after pre-treatment with GLA or PIN in ELOVL5 siRNA silenced EA.hy926 cells.Plant PUFAs (GLA and PIN) demonstrate anti-inflammatory effects in this model using endothelial cells, but are less potent than EPA or DHA. Anti-inflammatory effects of GLA and PIN may be due to their elongation metabolites; DGLA and ETrA.

GLA supplementation regulates PHD2 mediated hypoxia and mitochondrial apoptosis in DMBA induced mammary gland carcinoma.

The aim of the present study is to evaluate the effect of gamma linolenic acid (GLA) on mitochondrial mediated death apoptosis, hypoxic microenvironment and cholinergic anti-inflammatory pathway against 7, 12-dimethylbenz (a) anthracene (DMBA) induced mammary gland carcinoma. The effects of GLA were evaluated morphologically and biochemically against DMBA induced mammary gland carcinoma. The metabolic study was done for evaluation of biomarkers using 1H NMR. The present study was also verified through immunoblotting and qRT-PCR studies for the evaluation of various pathways. GLA treatment has a delineate implementation upon morphology of the tissues when evaluated through carmine staining, hematoxyline and eosin staining and scanning electron microscopy. GLA also demarked a commendatory proclamation of the fifteen key serum metabolites analogous with amino acid metabolism and fatty acid metabolism when recognized through1H NMR studies. The immunoblotting and qRT-PCR studies accomplished that GLA mediated mitochondrial death apoptosis, curtail hypoxic microenvironment along with hindrance of de novo fatty acid synthesis and also mediate the cholinergic anti-inflammatory pathway to proclaim its anticancer effects.

Effect of gamma linolenic acid pretreatment on diabetic neuropathy in rats

Background: The present study was planned to evaluate the preventive effects of gamma linolenic acid (GLA) on STZ induced diabetic neuropathy Methods: Streptozotocin (STZ) induced diabetic neuropathy in rats was monitored by measuring blood sugar levels, body weight, motor nerve conduction velocity (MNCV) and nociception. Forty rats were divided into 4 groups of 10 each. Group 1: control (vehicle), Group 2: STZ (50 mg/kg, i.v., single injection), Group 3: Gamma linolenic acid (50 mg/ kg, p.o., daily + STZ), Group 4: STZ + Insulin (4 units/kg, s.c., bid). Similar protocol was used for other parameters also. Results: Gamma linolenic acid pretreatment failed to reduce blood sugar levels in diabetic rats but prevented deterioration of motor nerve conduction velocity as compared to STZ diabetic rats. A significant weight gain was observed in STZ diabetic rats pretreated with GLA as compared to rats received STZ alone. Hyperalgesia induced by STZ was antagonized by GLA Conclusions: Thus gamma linolenic acid prevents the development of neuropathic changes induced by STZ in rats.

Gamma Linolenic Acid Exerts Anti-Inflammatory and Anti-Fibrotic Effects in Diabetic Nephropathy

PurposeThis study was undertaken to investigate the effects of gamma linolenic acid (GLA) on inflammation and extracellular matrix (ECM) synthesis in mesangial and tubular epithelial cells under diabetic conditions.Materials and MethodsSprague-Dawley rats were intraperitoneally injected with either a diluent [n=16, control (C)] or streptozotocin [n=16, diabetes (DM)], and eight rats each from the control and diabetic groups were treated with evening primrose oil by gavage for three months. Rat mesangial cells and NRK-52E cells were exposed to medium containing 5.6 mM glucose and 30 mM glucose (HG), with or without GLA (10 or 100 µM). Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin (FN) mRNA and protein expression levels were evaluated.ResultsTwenty-four-hour urinary albumin excretion was significantly increased in DM compared to C rats, and GLA treatment significantly reduced albuminuria in DM rats. ICAM-1, MCP-1, FN mRNA and protein expression levels were significantly higher in DM than in C kidneys, and these increases were significantly abrogated by GLA treatment. In vitro, GLA significantly inhibited increases in MCP-1 mRNA expression and protein levels under high glucose conditions in HG-stimulated mesangial and tubular epithelial cells (p<0.05, respectively). ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1.ConclusionGLA attenuates not only inflammation by inhibiting enhanced MCP-1 and ICAM-1 expression, but also ECM accumulation in diabetic nephropathy.

Scientific Opinion on the substantiation of health claims related to gamma linolenic acid and maintenance of joints (ID 494, 637, 1774, 2098), weight maintenance following weight loss (ID 496), maintenance of peripheral blood flow (ID 638), maintenance of normal blood pressure (ID 1771), maintenance of normal blood cholesterol concentrations (ID 1771) and maintenance of bone (ID 1774) pursuant to Article

Scientific Opinion on the substantiation of health claims related to gamma linolenic acid and maintenance of joints (ID 494, 637, 1774, 2098), weight maintenance following weight loss (ID 496), maintenance of peripheral blood flow (ID 638), maintenance of normal blood pressure (ID 1771), maintenance of normal blood cholesterol concentrations (ID 1771) and maintenance of bone (ID 1774) pursuant to Article

The Effect of Isoflavone and Gamma-linolenic Acid Supplementation on Serum Lipids and Menopausal Symptoms in Postmenopausal Women

This study was performed to examine the combined effects of gamma linolenic acid and isoflavone supplementation on menopausal symptoms and serum lipids in 73 postmenopausal women. A total subjects were randomly assigned to isoflavone (30 ㎎) + gamma-linolenic acid (110 ㎎) group or placebo group. We measured menopausal symptoms by modified Kupperman Index (KI) and oxidized LDL, lipid peroxides, blood components and anthropometric parameters before and after the 12 week intervention period. After the 12 weeks of supplementation, supplement group and placebo group showed a significant reduction of modified kupperman index (p < 0.001). Isoflavone (30 ㎎) + gamma-linolenic acid (110 ㎎) supplement group showed a significant reduction of oxidized LDL cholesterol concentration (p = 0.006) whereas placebo group did not show significant change. Isoflavone and gamma-linolenic acid consumption did not significantly affect plasma concentrations of total, LDL, HDL cholesterol, triglyceride, apo A1, B and blood components. The result of present study demonstrated the supplementation of 30 ㎎ isoflavone and 110 ㎎ gamma-linolenic acid per day for 12 weeks may protect LDL cholesterol from oxidative stress.

Induction of apoptosis in K562/ADM cells by gamma-linolenic acid involves lipid peroxidation and activation of caspase-3

Numerous studies have revealed that gamma-linolenic acid (GLA) possesses effective tumoricidal properties while not inducing damage to normal cells or creating harmful systemic side effects. It can exert anti-tumor efficacy against a variety of cancers including leukemia. However, little is known about the effects of GLA on leukemia resistant to chemotherapy, emerging as a serious clinical problem. The present study tested GLA-induced apoptosis in K562/ADM multidrug-resistant (MDR) leukemic cells and investigated its possible mechanisms. Using cell viability, fluorescent staining of nuclei, flow cytometric Annexin V/PI double staining and lactate dehydrogenase (LDH) release, we found that GLA could inhibit cell growth and induce apoptosis and secondary necrosis. The results showed that incubation with GLA concentrations of 10–60 μg/ml caused a dose- and time-dependent decrease of K562/ADM cell viability, and the IC 50 value was 50.5 μg/ml at 24 h and 31.5 μg/ml at 48 h. Flow cytometry using Annexin V/PI double staining assessed apoptosis, necrosis and viability. Typical apoptotic nuclei were shown by staining of K562/ADM cells with DNA-binding fluorochrome Hoechst 33342, characterized by chromatin condensation and nuclear fragmentation. On the other hand, after treated K562/ADM cells with 20 μg/ml GLA for 48 h and with 40 μg/ml GLA for 12 h, the LDH release significantly increased, indicated losses of plasma membrane integrity and presence of necrosis. Further, the inhibition of GLA-induced apoptosis by a pan-caspase inhibitor (z-VAD-fmk) suggested the involvement of caspases. The increase of caspase-3 activity with GLA concentration confirmed its role in the process. The results also showed that the malondialdehyde (MDA) content was also significantly elevated, and antioxidant BHT could block GLA cytotoxity, indicating the cytotoxity induced by GLA may be due to lipid peroxidation.

Properties of Cholesterol-reduced Butter and Effect of Gamma Linolenic Acid Added Butter on Blood Cholesterol

The present study was carried out to develop cholesterol-reduced and gamma linolenic acid (GLA)-added butter and to examine the changes in chemical and sensory properties, and cholesterol lowering effect of GLA addition. The cholesterol removal rate reached 93.2% by β-cyclodextrin in butter before GLA addition. The thiobarbituric acid value of cholesterol-reduced and GLA-added butter increased slowly up to 4 week and plauteaued thereafter. TBA value was significantly increased with 2% GLA addition, compared with no GLA addition. The production of short-chain free fatty acids (FFA) increased with storage in all treatments. From 4 weeks storage, the amount of short-chain FFA in 2% GLA-added group was significantly higher than those in other groups. Among sensory characteristics, color, greasiness and overall acceptability were mostly affected by GLA addition, however, the rancidity value of 2% GLA addition was significantly different from those of control and GLA-unadded and cholesterol-reduced butter at 0, 6 and 8 week storage. Among groups, no difference was found in texture in all storage periods. The smallest increase of total blood cholesterol in rats was found in the group fed 2% GLA-added and cholesterol-reduced butter for 8 week, compared with that in controls. The present results showed the possibility of cholesterol-reduced and GLA-added butter development without much difference in chemical, rheological and sensory properties, and indicated a slow increase effect on blood total cholesterol in rats. (Asian-Aust. J. Anim. Sci. 2005. Vol 18, No. 11 : 1646-1654)

Effect of dietary GLA+/-tamoxifen on the growth, ER expression and fatty acid profile of ER positive human breast cancer xenografts.

Gamma linolenic acid (GLA) possesses a number of selective anti-tumour properties including modulation of steroid receptor structure and function. We have investigated the effect of dietary GLA on the growth, oestrogen receptor (ER) expression and fatty acid profile of ER+ve human breast cancer xenografts. Experimental diets A, B, C, D were commenced after subcutaneous implantation of 40 female nude mice with the MCF-7 B1M cell line (Group A = control diet: B = control diet + GLA supplement: C = control diet + tamoxifen: D = control diet + GLA + tamoxifen; 10 mice/group). The mice were terminated when tumour cross-sectional area reached 250 mm(2). ER H-scores were assessed by immunohistochemical assay and fatty acid profiles by gas-liquid chromatography of termination tumour samples. Groups C and D displayed significantly slower tumour growth (p =.0002, p =.0006) with trend for slower growth in B (p =.065) compared to control Group A. ER was significantly reduced in all groups compared to A (p <.0001) with Group D (combined therapy) displaying markedly lower ER expression than with either therapy alone (p =.0002). There were significantly raised levels of tumour GLA and metabolites in the two groups (B and D) receiving GLA (p <.0001). This xenograft model of ER+ve breast cancer has demonstrated significantly lower tumour ER expression in those groups receiving GLA, an effect which appears to be additive to the reduced ER expression resulting from tamoxifen alone. The effects of GLA on ER function and the possibility of synergistic inhibitory action of GLA with tamoxifen via enhanced down-regulation of the ER pathway require further investigation.

Effects of gamma-linolenic acid and docosahexaenoic acid in formulae on brain fatty acid composition in artificially reared rats.

This study evaluated the effects of dietary supplementation with gamma-linolenic acid (GLA, 18:3n-6) and docosahexaenoic acid (DHA, 22:6n-3) on the fatty acid composition of the neonatal brain in gastrostomized rat pups reared artificially from days 5-18. These pups were fed rat milk substitutes containing fats that provided 10% linoleic acid and 1% alpha-linolenic acid (% fatty acids) and, using a 2x3 factorial design, one of two levels of DHA (0.5 and 2.5%), and one of three levels of GLA (0.5, 1.0, and 3.0%). A seventh artificially reared group served as a reference group and was fed 0.5% DHA and 0.5% arachidonic acid (AA, 20:4n-6); these levels are within the range of those found in rat milk. The eighth group, the suckled control group, was reared by nursing dams fed a standard American Institute of Nutrition 93M chow. The fatty acid composition of the phosphatidylethanolamine, phosphatidylcholine, and phosphatidylserine/phosphatidylinositol membrane fractions of the forebrain on day 18 reflected the dietary composition in that high levels of dietary DHA resulted in increases in DHA but decreases in 22:4n-6 and 22:5n-6 in brain. High levels of GLA increased 22:4n-6 but, in contrast to previous findings with high levels of AA, did not decrease levels of DHA. These results suggest that dietary GLA, during development, differs from high dietary levels of AA in that it does not lead to reductions in brain DHA.

Comparative anti-mitotic effects of lithium gamma-linolenate, gamma-linolenic acid and arachidonic acid, on transformed and embryonic cells

The effects of gamma-linolenic acid (GLA), the lithium salt of gamma-linolenic acid (LiGLA) and arachidonic acid (AA) were compared at doses of 50 μg/ml for periods of 6 and 24 h on cell cycle progression and apoptosis induction in transformed and in normal cells. In WHCO3 (oesophageal cancer) cells and on primary embryonic equine lung cells, we found LiGLA to be the most effective in apoptosis induction. After 24 h, 94% of the WHCO3 cancer cells and 44% of the primary embryonic equine lung cells exposed to LiGLA were apoptotic. The WHCO3 cancer cells were also very susceptible to the apoptosis-inducing effects of AA (56%) and GLA (44%), whereas the embryonic equine lung cells were much less affected by these two fatty acids. After 6 h exposure to all three compounds, most of the cycling WHCO3 cancer cells were blocked in S-phase. After 24 h treatment, some of the S-phase cells exposed to AA and GLA were apparently able to move into the G2/M phase, the LiGLA exposed cells were mostly apoptotic and no cycling cells were present. The primary embryonic equine lung cells were fairly resistant to the cytotoxic effects of GLA and AA. From our studies we conclude that, although LiGLA was the most toxic to the cancer cells, it is apparently less selective, compared to AA and GLA, in the killing of cancer and normal cells. It would also appear that the lithium might have added to the cytotoxic effects of LiGLA. The mechanism needs to be clarified.

P066 Protective and regenerative effects of gammalinolenic acid on atopic skin

P066 Protective and regenerative effects of gammalinolenic acid on atopic skin

Gamma Linolenic Acid Regulates Expression of Maspin and the Motility of Cancer Cells

Maspin, mammary serine protease inhibitor, is a recently identified tumour suppressor and has a profound effect on cell motility. This study examined the effect of gamma linolenic acid (GLA), an essential fatty acid (EFA) with anticancer properties, on the expression of maspin and motility of cancer cells. Six human cell lines including colon cancer, mammary cancer, and melanoma were used. Expression of maspin protein was determined by immunocytochemistry & Western blotting. Maspin mRNA was detected with reverse transcription-PCR (RT-PCR). Four of the six cell types expressed maspin with MDA MB 231 and ECV304 (endothelial cell) being negative. Treatment of these maspin positive cells with gamma linolenic acid (GLA) resulted in a concentration dependent stimulation of the expression of maspin protein with the effects seen as early as 4 hours. Linoleic acid had an inhibitory effects. Alpha linolenic acid and arachidonic acid had no significant effect. The mRNA levels from cells treated with GLA was seen to increase as shown by RT-PCR. Cell motility, monitored with time-lapse video recording and Hoffmann microscopy, showed a marked reduction in terms of spreading and migration on extracellular matrix coated surface. This reduction was reversed with anti-maspin antibody. It is concluded that GLA, a member of then-6 series of EFAs, up-regulates the expression of maspin which is associated with a reduction in the motility of cancer cells.

Effect of gamma-linolenic acid on plasma and membrane lipids and renal prostaglandins in old subjects: A. Hornych,∗ F. Girault, S. Oravec,∗ B. Forette,∗∗ D.F. Horrobin, Inserm U-430, Broussais Hospital, ∗ St. Perine Hospital, Paris, France and ∗∗ Scotia Research Institute, Stirling, Scotland

Effect of gamma-linolenic acid on plasma and membrane lipids and renal prostaglandins in old subjects: A. Hornych,∗ F. Girault, S. Oravec,∗ B. Forette,∗∗ D.F. Horrobin, Inserm U-430, Broussais Hospital, ∗ St. Perine Hospital, Paris, France and ∗∗ Scotia Research Institute, Stirling, Scotland

Growth Suppression of Hamster Flank Organs by Topical Application of γ-Linolenic and Other Fatty Acid Inhibitors of 5α-Reductase

Certain unsaturated aliphatic fatty acids, such as gamma-linolenic acid, inhibit 5alpha-reductase activity in vitro and in vivo. Hamster flank organ growth, as measured by the increase in the area of pigmented macule, is dependent on androgen. When one of the paired flank organs of a castrated hamster was treated topically with testosterone, the treated organ, but not the contralateral flank organ, became larger and darker. Topical application of gamma-linolenic acid to the testosterone-treated flank organ suppressed this testosterone effect. Other fatty acids that were not inhibitors of 5alpha-reductases were not active. Topical treatment of hamster flank organs with 5alpha-dihydrotestosterone also stimulated the growth of the organ. This 5alpha-dihydrotestosterone-dependent activity, however, was not significantly affected by gamma-linolenic acid, suggesting that flank organ growth was dependent on 5alpha-dihydrotestosterone and that gamma-linolenic acid acted by inhibiting 5alpha-reductase. With intact male hamsters, the endogenous androgen-dependent growth of flank organs is also suppressed by topical treatment with gamma-linolenic acid. The effect of gamma-linolenic acid is localized at the site of its application; topical application of gamma-linolenic acid did not affect the androgen-dependent growth of other organs such as testis, epididymis, seminal vesicle, and prostate. gamma-Linolenic acid, with low toxicity and absence of systemic effect, therefore may be potentially useful for treatment of androgen-dependent skin disorders.

Effects of gamma-linolenic acid and arachidonic acid on cell cycle progression and apoptosis induction in normal and transformed cells

The effects of arachidonic acid (AA) and gamma-linolenic acid (GLA) on cell cycle progression and apoptosis induction, using flow cytometry, were compared on normal human skin fibroblasts, strain HSF43 with wild type (wt) p53, large T antigen transformed HSF43 cells (line E8T4) with non functional p53, and on two lymphoblast cell lines, TK6 with wt p53 and WTK1 with mutant p53. AA and GLA caused similar dose (50, 75 and 100 μg/ml AA and GLA) and time dependent (24 and 48 h) induction of apoptosis in each cell line. The degrees of the response of the four cell lines were, however, different. The normal HSF43 cells were most resistant against apoptosis induction and the WTK1 cells most susceptible. The apoptosis induction appeared to be independent of functional p53. Cell cycle progression was also similarly affected by AA and GLA in the two cell types. In the fibroblast type cells (HSF43 and E8T4) S- and G 2/M-phase arrests were evident after 48 h exposure to AA and GLA, and in the lymphoblast cell lines (TK6 and WTK1) the cells were arrested in the G 1-phase.

Gamma linolenic acid regulates gap junction communication in endothelial cells and their interaction with tumour cells

Tumour-endothelial cell adhesion forms a key role in the establishment of distant metastases. This study examined the effect of gamma linolenic acid (GLA), an anti-cancer polyunsaturated fatty acid (PUFA), on both the gap junction communication of human vascular endothelial cells and tumour cell-endothelial interactions. By using scrape loading of Lucifer yellow dye, we showed that GLA at non-toxic levels increased Lucifer yellow transfer, indicating improved gap junction communication. The fatty acid also corrected the communication that was reduced by the mitogenic and motogenic factor HGF/SF. GLA inhibited the tyrosine phosphorylation of connexin-43, a protein that formed gap junction in this cell. When human tumour cells were added to quiescent or HGF/SF-activated endothelial cells, the presence of GLA reduced adhesion of tumour cells to the endothelium. It is concluded that GLA reduces tumour-endothelium adhesion, partly by improved gap junction communications of the endothelium.

Inhibition of membrane ruffling and ezrin translocation by gamma linolenic acid

Membrane ruffling of a tumour cell is correlated with its motile and metastatic behaviour. This study examined the effect of gamma linolenic acid (GLA), an anti-cancer agent, on HGF/SF induced membrane ruffling in the human cancer cell line, HT115. HGF induced a rapid appearance of membrane ruffling which was related to increased motility and the tyrosine phosphorylation and translocation of ezrin, a membrane-cytoskeleton linker protein. The presence of GLA significantly inhibited both the membrane ruffling and cell motility of the tumour cells, at sub-toxic concentrations. Western blotting revealed that the tyrosine phosphorylation of ezrin was inhibited by GLA. The translocation ezrin from cytosol and generalised areas of cell membrane to ruffled areas of the membrane induced by HGF/SF was also inhibited as shown by both indirect immunofluorescence and transmission electron microscopy. It is concluded that GLA inhibits HGF/SF induced membrane ruffling via its effect on ezrin, and this provides a further molecular explanation for the anti-tumour action of GLA.

Gamma linolenic acid inhibits tyrosine phosphorylation of focal adhesion kinase and paxillin and tumour cell matrix interaction

Gamma linolenic acid (GLA) is an anti-cancer agent recently reported to inhibit tumour cell-matrix attachment. This study examined the effects of GLA on the adhesion of two tumour cell lines, HT115 (human colon) and MDA MB 231 (human breast), to an extracellular matrix, Matrigel. The action of GLA on focal adhesion kinase(FAK) and paxillin was also investigated. Following cell adhesion to Matrigel in control experiments, both FAK and paxillin were quickly tyrosine phosphorylated and become concentrated at focal adhesion areas. Inclusion of GLA resulted in an inhibition of the tyrosine phosphorylation of both FAK and paxillin leading to a reduced attachment of both cell types to Matrigel. FAK and paxillin were also less well distributed in the focal adhesions compared with the controls. It is concluded, therefore, that GLA inhibits tumour-matrix adhesion via the inhibition of FAK and paxillin tyrosine phosphorylation.