rumenic-acid and Colonic-Neoplasms

Cancer cachexia is characterized by muscle and adipose tissue wasting caused partly by chronic, systemic inflammation. Conjugated linoleic acids (CLAs) are a group of fatty acids with various properties including anti-inflammatory cis9, trans11 (c9t11)-CLA and lipid-mobilizing trans10, cis12 (t10c12)-CLA. The purpose of this study was to test whether dietary supplementation of a c9t11-CLA-rich oil (6:1 c9t11:t10c12) could attenuate wasting of muscle and adipose tissue in colon-26 adenocarcinoma-induced cachexia in mice.. Loss of body weight, muscle and adipose tissue mass caused by tumors were not rescued by supplementation with the c9t11-CLA-rich oil. In quadriceps muscle, c9t11-CLA-rich oil exacerbated tumor-induced gene expression of inflammatory markers tumor necrosis factor-α, IL-6 receptor and the E3 ligase MuRF-1 involved in muscle proteolysis. In epididymal adipose tissue, tumor-driven delipidation and atrophy was aggravated by the c9,t11-CLA-rich oil, demonstrated by further reduced adipocyte size and lower adiponectin expression. However, expression of inflammatory cytokines and macrophage markers were not altered by tumors, or CLA supplementation.. These data suggest that addition of c9t11-CLA-rich oil (0.6% c9t11, 0.1% t10c12) in diet did not ameliorate wasting in mice with cancer cachexia. Instead, it increased expression of inflammatory markers in the muscle and increased adipose delipidation.

Topics: Adenocarcinoma; Adipocytes; Adiponectin; Adipose Tissue, White; Animals; Atrophy; Cachexia; Cell Size; Colonic Neoplasms; Diet; Gene Expression Regulation; Inflammation Mediators; Linoleic Acids, Conjugated; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Muscle Proteins; Neoplasm Transplantation; Quadriceps Muscle; Random Allocation; RNA, Messenger; Tripartite Motif Proteins; Ubiquitin-Protein Ligases

Beta-lactoglobulin (beta-LG) is a member of the lipocalin protein family and can bind a variety of hydrophobic molecules, such as fatty acids, in vitro. In this study, a potential colon-targeted antitumor drug was developed using bovine beta-LG as a carrier loaded with cis-9, trans-11 conjugated linoleic acid (CLA). The intrinsic tryptophan fluorescence intensity of beta-LG monitored by spectrofluorometer showed that 2.46 mol of CLA can be bound per mole of beta-LG. Dynamic light scattering showed the formation of a beta-LG-CLA self-assembled complex with particle size of 170+/-0.08 nm. After treatment with gastrointestinal pH and digestive enzymes, beta-LG-CLA complex showed very good stability in gastrointestinal conditions in vitro, measured by zeta potential analyzer and sodium dodecyl sulfate PAGE, respectively. In an intestinal model in vitro, the concentration of CLA in Caco-2 cells was detected by reverse-phase HPLC, and the level of CLA in cells after treatment with beta-LG-CLA complex was significantly greater than after treatment with CLA, which means beta-LG served as a capsular vehicle of CLA for intracellular transport. According to cell proliferation assay, beta-LG-CLA complex can inhibit the viability of Caco-2 cells, and the inhibition rate is significantly greater than with the same concentration of CLA (100 microM). The study revealed that bovine beta-LG as a carrier binding with CLA can potentially be used for colon cancer therapy.

Topics: Animals; Caco-2 Cells; Cattle; Cell Proliferation; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Colonic Neoplasms; Electrophoresis, Polyacrylamide Gel; Humans; Intestinal Absorption; Lactoglobulins; Linoleic Acids, Conjugated

This study investigated the isomer-specific effects of cis-9,trans-11 (c9,t11) and trans-10,cis-12 (t10,c12) conjugated linoleic acid (CLA) on the metastasis of colon cancer cells in vitro and in vivo. Cell migration was examined by a Boyden chamber assay in SW480 cells. MMP-9 activity was monitored by gelatin zymography, and MMP-9 protein and mRNA levels were determined by Western blot and RT-PCR analysis, respectively, in SW480 cells. For the experimental metastasis, BALB/c mice were injected intravenously with CT-26 cells in the tail vein. Mice were fed a diet containing either no CLA or 0.1% c9,t11 or t10,c12 CLA for 4 weeks. In experimental metastasis, the numbers of pulmonary nodules were significantly lower in mice fed CLA isomers than in mice fed a control diet (P<.05). Results from the Boyden chamber assay revealed that c9,t11 CLA significantly inhibited cell migration (P<.05), whereas t10,c12 CLA had no effect on cell migration. The activity of MMP-9 was significantly inhibited by c9,t11 CLA (P<.05) but not by t10,c12 CLA. However, neither MMP-9 protein nor mRNA levels were altered by either of these CLA isomers. We have demonstrated that diets containing 0.1% c9,t11 and t10,c12 CLA were equally effective in inhibiting colon cancer cell metastasis in vivo. However, in vitro, only c9,t11 but not t10,c12 inhibited colon cancer cell migration and MMP-9 activity.

Topics: Animals; Cell Movement; Colonic Neoplasms; Linoleic Acids, Conjugated; Lung Neoplasms; Male; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred BALB C; Neoplasm Metastasis; Tumor Cells, Cultured