epiglucan and Melanoma

There are still not specified mechanisms how beta-glucan molecules are transported into cells. Supposing, beta-glucan toxicity against tumor cells may be related to the overexpression of the transporter responsible for the transport of glucose molecules in the cells. In this case, glucans - polymers composed of glucose units are much more up-taken by tumor than normal cells. Increased GLUT1 (Glucose Transporter Type 1) expression has been demonstrated earlier in malignant melanomas. GLUT1 expression promotes glucose uptake and cell growth in that cells. Also, in human melanoma tissues a significant correlation between GLUT1 expression and mitotic activity was found. The aim of the study was to verify if oat β-glucan (OβG) is delivered into cells by GLUT-1 membrane protein. To check it out we blocked GLUT1 transporters by an inhibitor WZB117 and then we investigated cells viability with and without reversible electroporation (EP). The obtained results bring us to elucidate the mechanism of transport of the OβG into the cells is GLUT-1 dependent and moreover can be supported by EP method.

Topics: Antineoplastic Agents; beta-Glucans; Cell Line, Tumor; Electroporation; Glucose; Glucose Transporter Type 1; Humans; Melanoma

The currently available data suggest that natural products may exert significant cytotoxic and immunomodulatory effects. Plant-derived chemotherapeutic agents such as taxol, etoposide or vincristine, currently used in cancer therapy, are prominent examples in this regard. However, there is a need for new and nat- ural anticancer compounds with low or without toxicity to normal cells. One of the active compounds responsible for the immune effects is β-glucan derived from cereals, fungi, seaweeds, yeasts and bacteria. The recent data suggest that β-glucans are potent immunomodulators with anticancer properties. Antitumor properties of fungi and yeast derived β-glucans have been widely recognized, but those polysaccharides are mostly insoluble, creating several problems especially in topical formulation. To overcome the issue of low water solubility, in the current study a more soluble β-glucan type from oats was chosen for the investigation of its antitumor activities. Cytotoxic effects were studied using a human melanoma cell line (Me45). The effect of electroporation on the antitumor activity of oat β-glucan was investigated as well. Cellular viability assessment, immuno-cytochemistry and immunofluochemistry were employed to evaluate biologic effects. Our results indicate strong anticancer properties of oat β-glucan, enhanced by electroporation.

Topics: Adult; Antineoplastic Agents, Phytogenic; Apoptosis; Avena; beta-Glucans; Caspase 12; Caspase 3; Cell Line, Tumor; Cell Survival; Cytochromes c; Dose-Response Relationship, Drug; Electrochemotherapy; Humans; Male; Melanoma; Phytotherapy; Plants, Medicinal; Skin Neoplasms; Solubility

In this study, the growth-inhibitory effect of polysaccharide (1,3)(1,4)-β-D-glucan from oat, Avena sativa L. grains was explored on the human skin melanoma HTB-140 cells in vitro. The oat β-D-glucan (OBG) exerted cytotoxic action on HTB-140 cells. After 24h of incubation, LD50 (concentration at which 50% of the cells were found dead) was obtained of 194.6 ± 9.8 μg/mL. The oat β-D-glucan caused a concentration-dependent increase of caspase-3/-7 activation and appearance of phosphatidylserine on the external surface of cellular membranes where it was bound to annexin V-FITC, demonstrating the induction of apoptosis. Intracellular ATP level decreased along with the mitochondrial potential, which suggested a mitochondrial pathway of apoptosis. A cell cycle analysis showed increase in the number of apoptotic cells, increase in the number of cells in G1 phase and decrease in the number of cells in G2/M. Although the detailed mechanism for the anti-tumor activity of the oat β-D-glucan still needs further investigation, this study provides preliminary insights into this direction along with perspectives of developing it as an anti-tumor agent.

Topics: Apoptosis; Avena; beta-Glucans; Cell Cycle; Cell Line, Tumor; Humans; Melanoma; Melanoma, Cutaneous Malignant; Plant Extracts; Skin Neoplasms

Anticancer properties of 1-3, 1-4 oat beta glucan are under intensive investigation now. Antitumor characteristic of fungi and yeast beta-glucans have been widely recognized, but those polysaccharides are mostly insoluble which creates several problems especially in topical formulation. Also high molecular weight oat beta-glucans reveal high viscosity which restricts its application. According to those problems in the current study the antitumor activities of low molecular weight beta-glucan derived from oats were investigated in cancer cells: Me45, A431 and normal HaCaT and murine macrophages P388/D1. The low molecular weight beta-glucan from oat significantly deceased cancer cells viability, while for the normal cells it was non-toxic. It was observed that with the increasing incubation time and the beta-glucan concentration the cancer cells viability significantly deceased. Furthermore for the normal cells the low molecular weight beta-glucan from oat was non-toxic. Immunocytochemical ABC analysis showed that beta-glucan induced strong expression of caspase-12 in both cancer cell lines, while in HaCaT cells ABC reaction was significantly lower and in P388/D1 cell line ABC reaction was negative. Our preliminary studies show strong anti-tumor properties of new low molecular weight beta-glucan from oat and at the same time no toxicity for normal cells.

Topics: Adult; Animals; Antineoplastic Agents, Phytogenic; Avena; beta-Glucans; Caspase 12; Cell Line, Tumor; Cell Survival; Drug Screening Assays, Antitumor; Humans; Macrophages; Male; Melanoma; Mice; Molecular Weight; Skin Neoplasms

Both moderate exercise and the soluble fiber beta-glucan can have beneficial effects on the initiation and growth of tumors, but the data are limited, and there is no information on their combined effects. This study tested the independent and combined effects of short-term moderate-exercise training and the soluble oat fiber beta-glucan (ObetaG) on the metatastic spread of injected tumor cells and macrophage antitumor cytotoxicity. Male C57BL/6 mice were assigned to one of four groups: exercise (Ex)-H2O, Ex-ObetaG, control (Con)-H2O, or Con-ObetaG. ObetaG was fed in the drinking water for 10 days before tumor administration and death. Exercise consisted of treadmill running (1 h/day) for 6 days. After rest or exercise on the last day of training, syngeneic B16 melanoma cells (2 x 10(5)) were administered via intravenous injection (n = 8-11 per group). Lungs were removed 14 days later, and tumor foci were counted. Additional mice (n = 8 per group) were killed, and peritoneal macrophages were assayed for cytotoxicity against the same mouse tumor cell line at various effector-to-target ratios. Both moderate exercise and ObetaG decreased lung tumor foci and increased macrophage cytotoxicity. However, there were no differences in lung tumor foci and macrophage cytotoxicity between Ex-ObetaG and either Ex-H2O or Con-ObetaG. These data suggest that, although not additive in their effects, both short-term moderate-exercise training and consumption of the soluble ObetaG can decrease the metatastic spread of injected B16 melanoma cells, and these effects may be mediated in part by an increase in macrophage cytotoxicity to B16 melanoma.

Topics: Administration, Oral; Animals; beta-Glucans; Combined Modality Therapy; Cytotoxicity, Immunologic; Dietary Supplements; Exercise Therapy; Lung Neoplasms; Macrophage Activation; Male; Melanoma; Mice; Mice, Inbred C57BL; Physical Conditioning, Animal; Treatment Outcome

Macrophages obtained from animals treated with beta-1,3-D-glucan-derivatized plastic beads were greatly stimulated, as judged by morphology, esterase release, and cytostatic effect on L-929 tumour cells in vitro. The pretreatment of mice with such beads conferred an apparent absolute local resistance to an otherwise lethal pneumococcal infection but had no effect on the growth of intraperitoneal AA ascites sarcoma. Moreover, peritoneal cells from animals pretreated with glucan beads did not protect the animals in a Winn assay.

Topics: Animals; beta-Glucans; Cell Division; Cell Line; Esterases; Glucans; Leukemia; Macrophage Activation; Macrophages; Melanoma; Mice; Mice, Inbred C57BL; Microspheres; Pneumococcal Infections