gamma-linolenic-acid and Colonic-Neoplasms

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

This study examined the effect of n-6 polyunsaturated fatty acids (PUFAs) on the expression of nm-23, a metastasis-suppressor gene, in two highly invasive human cancer cell lines, HT115 and MDA MB 231. A range of n-6 and n-3 PUFAs were tested. We report that while linoleic acid and arachidonic acid reduced the expression of nm-23-H1, gamma linolenic acid (GLA) and its soluble lithium salt markedly increased the expression of the molecules. The stimulation of the expression of nm-23 by GLA was seen at both protein and mRNA levels. Up-regulation of nm-23 was also associated with a reduction of the in vitro invasiveness of these cells. It is concluded that gamma linolenic acid (GLA) enhances the expression of nm-23. This contributes to the inhibition of the in vitro invasion of tumour cells.

Topics: Arachidonic Acid; Breast Neoplasms; Colonic Neoplasms; Drug Screening Assays, Antitumor; Eicosapentaenoic Acid; gamma-Linolenic Acid; Gene Expression Regulation, Neoplastic; Humans; Linoleic Acid; Monomeric GTP-Binding Proteins; Neoplasm Invasiveness; Neoplasm Proteins; NM23 Nucleoside Diphosphate Kinases; Nucleoside-Diphosphate Kinase; RNA, Messenger; RNA, Neoplasm; Transcription Factors; Tumor Cells, Cultured

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.

Topics: Breast Neoplasms; Cell Adhesion; Cell Communication; Cell Line; Colonic Neoplasms; Connexin 43; Endothelium, Vascular; Fatty Acids; Fluorescent Dyes; gamma-Linolenic Acid; Gap Junctions; Hepatocyte Growth Factor; Humans; Isoquinolines; Kinetics; Phosphorylation; Precipitin Tests; Tumor Cells, Cultured

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.

Topics: Breast Neoplasms; Cell Line; Cell Movement; Colonic Neoplasms; Endothelium, Vascular; Fatty Acids, Nonesterified; Female; gamma-Linolenic Acid; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; Humans; Kinetics; Melanoma; Polymerase Chain Reaction; Protein Biosynthesis; Proteins; RNA, Messenger; Serine Proteinase Inhibitors; Serpins; Transcription, Genetic; Tumor Cells, Cultured

We examined the effect of gamma-linolenic acid (GLA) supplementation on the growth and fatty acid composition of three human tumor cell lines (the neuroblastoma CHP-212, the tubal carcinoma TG, and the colon carcinoma SW-620), in order to evaluate the relationship between GLA-induced tumor cell death and the distribution of fatty acids in tumor cells. At the highest GLA concentrations (10 and 20 micrograms/ml), the DNA synthesis was completely abolished; at 5 micrograms/ml GLA only SW-620 cells did not proliferate, while CHP-212 and TG cells showed a residual [3H]-thymidine incorporation. GLA levels were very low in cells grown in control medium; GLA supplementation caused a significant incorporation of GLA itself in all the cell lines at each concentration. In TG and CHP-212 cells, GLA was metabolized, although to a different extent, to dihomo-gamma linolenic acid and arachidonic acid. SW-620 cells neither elongated nor desaturated the incorporated GLA. The highest cytostatic effect was reached when GLA was not transformed into its metabolites, suggesting that the GLA toxicity to tumor cells is not dependent on metabolites but is due to GLA itself.

Topics: Cell Division; Colonic Neoplasms; Fallopian Tube Neoplasms; Fatty Acids; Female; gamma-Linolenic Acid; Humans; Neuroblastoma; Tumor Cells, Cultured

The objective of the present study was to investigate the effect of membrane fatty acid (FA) composition on the activity of phospholipase C (PLC) in HT-29 human colon cancer cells. The membrane FA composition was altered by supplementing cultured cells with FAs of different composition. The FAs were stearic acid (18:0; SA), gamma linolenic acid (18:3 omega 6; gamma LnA); alpha linolenic acid (18:3 omega 3; alpha LnA;); eicosapentaenoic acid (20:5 omega 3; EPA) and docosahexaenoic acid (22:6 omega 3; DHA). The fatty acids were supplemented as a FA/BSA complex. Cells supplemented with SA served as the control. Tumor growth was followed by counting the number of cells in culture. The results indicate that polyunsaturated fatty acid (PUFA) supplementation had no consistent effect on tumor growth from 1 day to another throughout the 15 days of growth. The fatty acid composition of membranes indicates that cells incorporated and modified the supplemented fatty acids by desaturation, elongation and retroconversion. The unsaturation index (UI) of membranes of cells supplemented with EPA and DHA was higher than other groups. PLC activity; measured in the absence of GTP gamma(S) in the assay mixture; was not influenced by membrane FA modification. However, in the presence of GTP gamma(S) PLC of cells supplemented with 18:3(omega 6) was the lowest among the groups. It has been shown that 18:3(omega 6) accumulated the most in the phosphatidylethanolamine (PE) fraction. There was a negative correlation between the activity of PLC in the presence of G protein activation and PE 18:3 (omega 6) content without affecting UI. It was concluded that G protein may be sensitive to the level of 18:3(omega 6) content and not to the general fluidity of the membranes.

Topics: alpha-Linolenic Acid; Animals; Cattle; Cell Membrane; Colonic Neoplasms; Dietary Fats; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Unsaturated; gamma-Linolenic Acid; GTP-Binding Proteins; Humans; Membrane Lipids; Neoplasm Proteins; Phosphatidylinositol Diacylglycerol-Lyase; Phosphoric Diester Hydrolases; Serum Albumin, Bovine; Signal Transduction; Stearic Acids; Tumor Cells, Cultured

In this study we have determined the effects of the n-6 essential fatty acid gamma-linolenic acid (GLA) on the motility and invasive/metastatic nature of the human colon cancer cell lines HT115, HT29 and HRT18. Cell motility was induced by hepatocyte growth factor/scatter factor (HGF/SF) and measured by both colony scattering and dissociation from carrier beads. Invasiveness was measured in vitro by cellular invasion into extracellular matrix. At concentrations up to 100 microM (which had no effect on cell growth over the duration of the experiments) both cell motility and invasion induced by HGF/SF were markedly reduced by GLA and its lithium salt. The attachment of these cells to the extracellular matrix components (Matrigel and fibronectin) was also inhibited. There were also changes in the cell-surface E-cadherin, but not fibronectin receptor at similar concentrations. It is concluded that n-6 essential fatty acids have the ability to inhibit both motility and invasiveness of human colon cancer cells, perhaps by modifying cell-surface adhesion molecules.

Topics: Arachidonic Acid; Cadherins; Cell Adhesion; Cell Line; Cell Movement; Colonic Neoplasms; Extracellular Matrix; gamma-Linolenic Acid; Hepatocyte Growth Factor; Humans; Linoleic Acid; Linoleic Acids; Neoplasm Invasiveness; Receptors, Fibronectin; Tumor Cells, Cultured

Several studies have demonstrated that certain essential fatty acids present a specific cytotoxicity for tumor cells. However, no investigation of this type has been performed on human colon cancer cells to date. This study investigated the effect of gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and prostaglandin (PG) E1 on the proliferation and metabolism of three human colon cancer cell lines: HT 29, HRT 18, and CACO 2. GLA, EPA and PGE1 all inhibited the proliferation of the three cell lines, but with a decreasing gradient of sensitivity: HRT 18 > HT 29 > CACO 2, and with different IC50 values. PGE1 was markedly less effective than the other two. GLA and EPA increased lipid peroxidation and membrane fluidity in a dose-dependent manner. The presence of indomethacin did not modify the effects of GLA and EPA. In addition, PGE1 had little effect on membrane fluidity and lipid peroxidation. The antitumoral effect thus does not appear to be mediated by PGE1. Addition of vitamin E decreased the effects of GLA and EPA, which supports the hypothesis of direct action by these fatty acids. In conclusion, while EPA and GLA have an antitumoral effect in vitro, their effect on primary cultures of normal human colon cells must be investigated to determine whether this effect is specific to tumoral cells, as has been observed for other cell types.

Topics: Alprostadil; Cell Division; Cell Line; Colonic Neoplasms; Cyclic AMP; Eicosapentaenoic Acid; gamma-Linolenic Acid; Humans; Linolenic Acids; Lipid Peroxidation; Membrane Fluidity; Tumor Cells, Cultured; Vitamin E