gamma-linolenic-acid and Lung-Neoplasms

The main therapies for cancer often results in many side effects and drug resistance. Gamma linolenic acid (GLA) is a kind of natural reagent with negligible cytotoxicity.. This work aims at detecting whether GLA possesses anti-cancer activity in NSCLC cells and elucidating the potential molecular mechanism.. Cytotoxicity of GLA was evaluated by MTT assay and soft agar colony formation method. Immunoblotting analysis examined the effect of GLA on protein expressions of cell proliferation markers (e.g., PCNA, Ki-67 and MCM2), pro-survival protein bcl-2, apoptosis-associated proteins (e.g., bax and cleaved caspase 3), HIF1α and VEGF. Wound healing assay and transwell invasion assay were performed to test the effect of GLA on hypoxia-induced cell migration and invasion. Cell transfection was used to overexpress HIF1α followed by the treatment of GLA to test the effect of HIF1α overexpression on the tumoricidal activity of GLA in NSCLC cell lines.. MTT and soft agar colony formation tests showed that GLA dose-dependently suppressed cell proliferation in both Calu-1 and SK-MES-1 cell lines. Immunoblotting analysis demonstrated that GLA suppressed protein expressions of PCNA, Ki-67, MCM2 and bcl-2, while GLA induced bax and cleaved caspase 3 expressions. Wound healing assay and transwell invasion assay revealed that GLA was very effective on the inhibition of NSCLC cell migration and invasion. Immunoblotting analysis and cell transfection method indicated that GLA inhibited hypoxia-induced cell proliferation and invasion by suppressing HIF1α-VEGF pathway.. GLA suppresses hypoxia-induced proliferation and invasion of NSCLC cells by inhibition of HIF1α pathway in vitro.

Topics: Antineoplastic Agents; bcl-2-Associated X Protein; Carcinoma, Non-Small-Cell Lung; Caspase 3; Cell Line, Tumor; Cell Movement; Cell Proliferation; gamma-Linolenic Acid; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Ki-67 Antigen; Lung Neoplasms; Minichromosome Maintenance Complex Component 2; Neoplasm Invasiveness; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Vascular Endothelial Growth Factors

Reactive oxygen intermediate (roi) generation was investigated in phagocytes of 39 patients undergoing pulmonary resection for lung cancer and 39 paired healthy controls. Generation of roi in monocytes and neutrophils was monitored using 2',7'-dichlorofluorescin diacetate. Activation associated with hydrophobic interactions was probed by analysis of phagocyte roi activation by arachidonic acid and gamma-linolenic acid. Patient roi was measured pre-operatively and 2 and 7 days post-operatively. Elevated (P < 0.01) roi production was detected in neutrophils of lung cancer patients. Surgery was associated with an increase (P < 0.05-P < 0.01) in phagocyte roi at 2 and 7 days post-op. Phagocyte roi was stimulated by arachidonic acid and gamma-linolenic acid (1-40 microM) both pre- and post-operatively. Differences in arachidonic acid and gamma-linolenic acid stimulation between patient and control and pre- and post-op patient phagocytes suggest arachidonic acid involvement in phagocyte activation during reactive responses to lung carcinoma and surgery.

Topics: Arachidonic Acid; Carcinoma, Bronchogenic; gamma-Linolenic Acid; Humans; Lung Neoplasms; Monocytes; Neutrophils; Pneumonectomy; Postoperative Period; Reactive Oxygen Species; Respiratory Burst

It has been reported that gamma-linolenic acid (GLA)-rich diets suppress mammary carcinogenesis and transplanted tumor growth and that GLA inhibits the growth of cultured human cancer cell lines. We compared the effects of dietary GLA and linoleic acid (LA) on the growth of MDA-MB-435 human breast cancer cells and their expression of the metastatic phenotype in vivo and in vitro. Athymic nude mice (30/dietary group) were fed isocaloric diets containing 20% (wt/wt) fat but providing 8% GLA or LA for 7 days, and 10(6) tumor cells were then injected into a thoracic mammary fat pad. The diets were continued for a further 11 weeks. The primary tumor growth rates were similar in mice from the two dietary groups; there was a nonstatistically significant trend for the incidence of macroscopic lung metastases and the total lung metastatic volumes to be higher in the GLA-fed mice (79% and 40.1 +/- 13.9 mm3) than in the LA-fed mice (64% and 15.5 +/- 5.4 mm3). The tumor cell phospholipids from the 8% GLA-fed mice contained significantly lower LA levels but higher arachidonic acid levels (both p < 0.001) than those from 8% LA-fed mice. Also the arachidonate-derived eicosanoids (prostaglandin E, leukotriene B4, and 5-, 12-, and 15-hydroxyeicosatetraenoic acids) were significantly higher in tumors from the 8% GLA group. Zymography showed higher 92-kDa type IV collagenase activity in tumors from 8% GLA-fed mice. In vitro, GLA and LA, at 0.5-2 micrograms/ml, stimulated MDA-MB-435 cell growth; 10 micrograms/ml was mildly inhibitory. Whereas LA stimulated tumor cell invasion and 92-kDa type IV collagenase production in vitro, GLA inhibited invasion and did not induce activity of the proteolytic enzyme. Our results do not support the hypothesis that supplementation with GLA would exert a beneficial effect on the progression of an existing breast cancer, perhaps because it is metabolized in vivo to arachidonate-derived eicosanoids that are known to be involved in the metastatic process.

Topics: Animals; Arachidonic Acid; Body Weight; Breast Neoplasms; Cell Division; Collagenases; Dietary Fats; Eicosanoids; Fatty Acids; Female; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Invasiveness; Phospholipids; Tumor Cells, Cultured

We have studied the effect of a gamma-linolenic acid (18:3 n-6, GLA)-supplemented diet on the growth of a human lung mucoepidermoid carcinoma (HLMC) implanted in athymic mice and on its uptake of human low density lipoproteins labeled with 99mTc (99mTc-LDL). Mice bearing the HLMC were divided into two experimental groups. One of them was administered a control diet (C diet) and the other one was given a diet supplemented with 25 mg GLA/g pellet (GLA diet) for three weeks (Table 1). A tumor growth inhibition with the GLA diet was evident at the second week of treatment, and a marked inhibition (56%) was reached at the end of the third week (Fig. 1). The GLA diet produced some changes in the total fatty acid composition of tumor, plasma and liver of host mice: GLA and arachidonic acid (20:4 n-6, AA) induced significant increases, whereas oleic (18:1 n-9, OA) and linoleic acids (18:2 n-6, LA) were decreased (Table 2). Tumors of those animals fed both diets were labeled by 99mTc-LDL, and no difference was observed in the ratio of tumor/liver and tumor/kidney uptake of host animal (Table 3). Results obtained using this experimental model suggest that the inhibitory effect of GLA on tumor growth is not related to the LDL tumor uptake.

Topics: Analysis of Variance; Animals; Carcinoma, Mucoepidermoid; Diet; Fatty Acids; Female; Food, Fortified; gamma-Linolenic Acid; Humans; Lipoproteins, LDL; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation; Organotechnetium Compounds

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

Polyunsaturated fatty acids killed incubated human breast, lung and prostate cancer cells at concentrations which had no adverse effects on normal human fibroblasts or on normal animal cell lines. The most consistent and selective effects were obtained with fatty acids containing 3, 4 and 5 double bonds. When human cancer cells and normal human fibroblasts were co-cultured in the absence of polyunsaturated fatty acids, the malignant cells overgrew the normal ones. When eicosapentaenoic acid (EPA, 20:5n-3), gamma-linolenic acid (GLA, 18:3n-6) or arachidonic acid (AA, 20:4n-6) were added to the co-cultures, the normal cells outgrew the malignant ones. These observations suggest that treatment of malignancy with polyunsaturated fatty acids may have considerable potential while being associated with a high level of safety.

Topics: alpha-Linolenic Acid; Animals; Breast Neoplasms; Cell Division; Cell Line; Cell Survival; Dogs; Fatty Acids, Unsaturated; Female; Fibroblasts; gamma-Linolenic Acid; Humans; Linolenic Acids; Lung Neoplasms; Male; Neoplasms; Prostatic Neoplasms