Antioxidant, anti-inflammatory and beneficial metabolic effects of botryosphaeran [(1→3)(1→6)-ß-d-glucan] are responsible for its anti-tumour activity in experimental non-obese and obese rats bearing Walker-256 tumours.

Botryosphaeran, a (1→3)(1→6)-ß-d-glucan, presents several beneficial activities, such as antiproliferative, hypoglycemic and antitumoural activities. This study evaluated the effects of botryosphaeran on oxidative stress, inflammation and metabolic activities in Walker-256 tumour-bearing non-obese and obese rats. Wistars rats were divided into four groups: control tumour (CT); control tumour + botryosphaeran (CTB); obese tumour (OT), and obese tumour + botryosphaeran (OTB). In ninth week, obese and non-obese rats were inoculated with 1 × 107 Walker-256 tumour cells and treated with botryosphaeran (30 mg/kg/d for 15 days). In 11th week, the following parameters were evaluated glycogen, glucose and lactate levels, pro-oxidant (TBARS) and antioxidant markers (superoxide dismutase [SOD]; catalase [CAT]; glutathione-S-transferase [GST]; reduced glutathione [GSH]; vitamin C) and cytokines. Obesity presented oxidative stress and inflammation, as demonstrated by high levels of TBARS, SOD and TNF-α, and lower levels of CAT, GSH and interleukin-10 (IL-10). Botryosphaeran significantly decreased TBARS and TNF-α and increased GST, GSH, vitamin C and IL-10 in the liver; increased SOD and vitamin C in tumour tissue; decreased TBARS in adipose tissue, and notably decreased the levels of glycogen and lactate in the tumour of CTB rats. Botryosphaeran promoted significant antioxidant, anti-inflammatory, and beneficial metabolic effects in Walker-256 tumour-bearing non-obese and obese rats, which contributed to its antitumour activity.

Botryosphaeran, a (1 → 3)(1 → 6)-ß-D-glucan, reduces tumor development and cachexia syndrome in obese male rats by increasing insulin sensitivity and FOXO3a activity.

Obesity is an important risk factor in tumor development. Botryosphaeran, a (1 â†’ 3)(1 â†’ 6)-ß-D-glucan, produced by the fungus Botryosphaeria rhodina (MAMB-05), is a high molecular mass, water-soluble exopolysaccharide. It consists of a main chain of (1 â†’ 3)-linked ß-d-glucose units, with a degree of branching of ~22% at carbon-6 with glucose and gentiobiose residues linked through ß-(1 â†’ 6)-bonds, and presents a triple helix conformation. Botryosphaeran presents anticlastogenic, antiproliferative, pro-apoptotic and anti-obesogenic activities. This study evaluated the effects of botryosphaeran on tumor development in obesity and analyzed its mechanism of action. Obesity was induced in male Wistar rats by a high-fat/high-sugar diet. After 9 weeks, rats were divided into two groups: Obese Tumor (OT) and Obese Tumor Botryosphaeran (OTB), and inoculated with 1 × 107 Walker-256 tumor cells, and treatment with botryosphaeran (30 mg/kg b.w./day via gavage for 15 days) commenced. On the 11th week, biological parameters, tumor development, metabolic profile, erythrogram and protein expression were evaluated. Botryosphaeran significantly reduced tumor growth, body-weight loss and cachexia. Furthermore, botryosphaeran decreased mesenteric fat and insulin resistance, corrected macrocytic anemia, and increased Forkhead transcription factor-3a (FOXO3a) activity. Our study demonstrated the potential role of botryosphaeran in the management of cancer in tumor-bearing obese rats by increasing insulin sensitivity and FOXO3a activity.

Tumor development in rats and cancer cachexia are reduced by treatment with botryosphaeran by increasing apoptosis and improving the metabolic profile.

AIMS: Cancer is a multifactorial disease characterized by an uncontrolled growth of cells that can lead to cachexia-anorexia syndrome. Botryosphaeran, a fungal (1 â†’ 3)(1 â†’ 6)-ß-D-glucan produced by Botryosphaeria rhodina MAMB-05, has presented antimutagenic, antiproliferative, pro-apoptotic, hypoglycemic and hypocholesterolemic effects. This study evaluated the effects of botryosphaeran (30 mg/kg b.w./day) on tumor development and cachexia syndrome in Walker-256 tumor-bearing rats, and also the metabolic and hematological profiles of these animals. MATERIALS AND METHODS: Male Wistar rats were divided into 3 groups: control (C), control tumor (CT) and control tumor botryosphaeran (CTB). On the first day, 1 × 107 Walker-256 tumor cells were inoculated subcutaneously into the right flank of the CT and CTB rats, and concomitantly treatment with botryosphaeran (30 mg/kg b.w./day) started. After the 15th day of treatment, biological parameters, tumor development, cachexia, glucose and lipid profiles, hemogram and protein expression were analyzed. KEY FINDINGS: Botryosphaeran significantly reduced tumor development (p = 0.0024) and cancer cachexia, modulated the levels of glucose, triglycerides and HDL-cholesterol, and corrected macrocytic anemia. Botryosphaeran also increased significantly the bax expression in the tumor tissue (p = 0.038) demonstrating that this (1 â†’ 3)(1 â†’ 6)-ß-D-glucan is increasing the apoptosis of tumor cells. p53, p27, bcl-2, caspase-3 and Forkhead transcription factor 3a (FOXO3a) protein expression were similar among the groups. SIGNIFICANCE: This study demonstrated that botryosphaeran was effective in decreasing tumor development and cachexia by direct and indirect mechanisms increasing apoptosis and improving the metabolic and hematological profiles.