laminaran and Colonic-Neoplasms

Polysaccharide fractions of alginate, laminarans and fucoidans were obtained from the brown alga Tauya basicrassa. Yields of alginate and laminarans were large (19.7 % and 5.62 %, respectively), whereas the content of fucoidans (0.52 %) was not significant. Alginate and laminarans had typical structures for those substances. Fucoidans were low- and medium-sulfated heterogeneous polysaccharides. The fucoidan fraction 1TbF1 was sulfated fucogalactan containing a backbone from 1,6-linked residues of β-d-galactopyranose with branches at C3 and C4, terminal fucose and galactose residues and fragments from 1,3-; 1,4-; and 1,2-fucose residues. Sulfate groups were found at positions 2 and 4 of fucose, and positions 2, 3 and 4 of galactose residues. Laminaran 2TbL was subjected to a sulfation to obtain the derivative 2TbLS with partial sulfation (46 %) at C2, C4 and C6. It was shown that 2TbL and 2TbLS inhibited colony formation of sensitize-tested colon cancer cells HT-29 and HCT-116 to X-ray radiation.

Topics: Antineoplastic Agents; Colonic Neoplasms; Glucans; Humans; Phaeophyceae; Polysaccharides; Radiation-Sensitizing Agents; Sulfates; Tumor Cells, Cultured; X-Rays

Laminarin, found in marine brown algae, is used as a carbohydrate reserve for phytoplankton; however, it is also used in traditional Chinese medicine, and has been shown to have several biological activities, including anticancer activities. In this study, we examined the mechanisms through which laminarin from Laminaria digitata induces apoptosis in HT-29 colon cancer cells, as well as the involvement of the ErbB signaling pathway. Cell viability assay revealed that laminarin induced cell death in a dose-dependent manner. Cell cycle analysis revealed that laminarin increased the percentage of cells in the sub-G1 and G2-M phase. Western blot analysis demonstrated that laminarin inhibited the heregulin-stimulated phosphorylation of ErbB2. A decrease in cellular proliferation was also observed; this was found to be dependent on ErbB, which activates c-Jun N-terminal kinase. These findings demonstrate the important role of the epidermal growth factor receptor in colon cancer tumorigenesis, and suggest the potential of laminarin as a bio-functional food with anticancer effects on human colon cancer.

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Cycle Proteins; Cell Line, Tumor; Colonic Neoplasms; ErbB Receptors; Gene Expression Regulation, Neoplastic; Glucans; HT29 Cells; Humans; Membrane Potential, Mitochondrial; Neuregulin-1; Phosphorylation; Polysaccharides; Proto-Oncogene Proteins c-akt; Signal Transduction

In recent years, algae have been highlighted as potential sources of anticancer agents. Laminarin is a molecule found in marine brown algae that has potentially beneficial biological activities. However, these activities have not been investigated. In the present study, we examined the effects of laminarin on HT-29 cells and analyzed its effect on the insulin-like growth factor (IGF-IR) signaling pathway. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays revealed that laminarin induced cell death in a dose-dependent manner. Western blotting showed that laminarin decreased mitogen-activated protein kinases (MAPK) and ERK phosphorylation. Decreased proliferation depended on IGF-IR, which was associated with the downregulation of MAPK/ERK. These results are important for understanding the roles of IGF-IR in colon cancer cell tumorigenesis, and suggest that laminarin shows activity against human colon cancer.

Topics: Antineoplastic Agents; Apoptosis; Colon; Colonic Neoplasms; Glucans; HT29 Cells; Humans; Mitogen-Activated Protein Kinases; Phaeophyceae; Phosphorylation; Polysaccharides; Signal Transduction; Somatomedins

Many scientific studies have shown that laminarin has anti-tumor effects, but the anti-tumor mechanism was unclear. The purpose of this study was to investigate the effect of laminarin on the induction of apoptosis in human colon cancer LOVO cells and the molecular mechanism involved. LOVO cells were treated with different concentrations of laminarin at different times. Morphology observations were performed to determine the effects of laminarin on apoptosis of LOVO cells. Flow cytometry (FCM) was used to detect the level of intracellular reactive oxygen species (ROS) and pH. Laser scanning confocal microscope (LSCM) was used to analyze intracellular calcium ion concentration, mitochondrion permeability transition pore (MPTP) and mitochondrial membrane potential (MMP). Western blotd were performed to analyze the expressions of Cyt-C, Caspase-9 and -3. The results showed the apoptosis morphology, which showed cell protuberance, concentrated cytoplasm and apoptotic bodies, was obvious after 72 h treatment. Laminarin treatment for 24 h increased the intracellular level of ROS and Ca²⁺; decreased pH value; activated intracellular MPTP and decreased MMP in dose-dependent manners. It also induced the release of Cyt-C and the activation of Caspase-9 and -3. In conclusion, laminarin induces LOVO cell apoptosis through a mitochondrial pathway, suggesting that it could be a potent agent for cancer prevention and treatment.

Topics: Antineoplastic Agents; Apoptosis; Calcium; Caspase 3; Caspase 9; Cell Line, Tumor; Colonic Neoplasms; Cytochromes c; Glucans; Humans; Hydrogen-Ion Concentration; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Polysaccharides; Reactive Oxygen Species; Signal Transduction

The effect of pleuran (beta-1,3-D-glucan isolated from the oyster mushroom Pleurotus ostreatus) on the antioxidant status of the organism and on the development of precancerous aberrant crypt foci (ACF) lesions in the colon is studied in the male Wistar rat. A diet containing either 10% pleuran or 10% cellulose was compared with a cellulose-free diet and both were found to significantly reduced conjugated diene content in erythrocytes and in liver. Particularly significant was the reduction of conjugated dienes in the colon following pleuran administration. Diets containing cellulose and pleuran reduced glutathione peroxidase (GSH-PX) activity and increased catalase activity in erythrocytes. Pleuran increased superoxide dismutase (SOD) and GSH-PX activity (compared with the cellulose diet), and glutathione reductase activity (compared with the cellulose-free diet) in liver; and both diets reduced glutathione levels significantly in the colon. ACF lesions developed in the colon of all animals fed a cellulose-free diet; however, the incidence was reduced to 64% and 60% following the cellulose and pleuran diets, respectively. The highest average count of the most frequent small ACF lesions--and highest total count--was seen in animals fed a cellulose-free diet. Although ACF lesions were reduced by the cellulose diet, the more significant reduction statistically (>50%) was achieved with the pleuran diet.

Topics: 1,2-Dimethylhydrazine; Animals; Antineoplastic Agents; Antioxidants; beta-Glucans; Colonic Neoplasms; Glucans; Male; Precancerous Conditions; Rats; Rats, Wistar

The purpose of this study was to investigate the combined antitumor effect of aminated beta-1,3-D-glucan (AG) and interferon-gamma (IFN-gamma) in an experimental liver metastasis model. Liver metastases were established by inoculation of C-26 colon carcinoma cells into the superior mesenteric vein of syngeneic mice. Treatment of mice started 24 hours after inoculation of tumor cells by daily intravenous injections of either AG, IFN-gamma, or a combination of both for a duration of 6 days. The resultant liver metastases were then quantified after an additional period of 11 days. Combination of IFN-gamma and AG inhibited the growth of liver metastases almost entirely. IFN-gamma was also very efficient, while AG alone did not exert any significant antitumor effect. These results, along with histological studies from mice receiving AG and IFN-gamma, indicated that activation and recruitment of liver macrophages may be a part of the mechanism responsible for the inhibition of metastatic growth observed in this study.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Carcinoma; Colonic Neoplasms; Drug Synergism; Female; Glucans; Interferon-gamma; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Metastasis; Recombinant Proteins

Nutrients not absorbed in the small bowel will form substrates for microbial growth in the colon which may have implication for the development of colon cancer. The aim of the present study was to investigate whether fibre-rich oat and barley diets increase the excretion of energy-supplying nutrients from the small bowel compared with a low-fibre wheat diet, and whether a possible increase could be related to the beta-glucan content. Nine ileostomy subjects were served four types of bread together with a low-fibre basal diet (12 g dietary fibre/d). The breads were based on either wheat flour (W diet, 7 g dietary fibre/d), oat bran (OB diet, 29 g dietary fibre/d), the same amount of oat bran with addition of beta-glucanase (EC 3.2.1.4) (OBE diet, 19 g dietary fibre/d) or a fibre-rich barley fraction (B diet, 35 g dietary fibre/d). An increased ileal excretion of starch was observed with the barley diet but no effect of the oat beta-glucan on starch recovery was found. The NSP + Klason lignin in the ileostomy effluents accounted only for 24, 31, 24 and 35% of the gross energy excretion in the W, OB, OBE and B diet periods respectively. A large part of the dry weight and energy (30, 21, 28 and 27%, in the W, OB, OBE and B diets respectively) in the effluents could not be identified as fat, protein, total starch or NSP + Klason lignin. This unidentified part was probably made up of oligosaccharides, endogenous losses and nutrient complexes. Methods for identifying and analysing these components should be developed and their role as substrates for colonic fermentation and colon cancer development ought to be investigated.

Topics: Adult; Aged; Antineoplastic Agents; Avena; beta-Glucans; Colon; Colonic Neoplasms; Dietary Fiber; Female; Glucans; Hordeum; Humans; Ileostomy; Male; Middle Aged; Starch; Triticum