Botryosphaeran, a (1 → 3)(1 → 6)-β-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 → 3)(1 → 6)-β-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 → 3)-linked β-d-glucose units, with a degree of branching of ~22% at carbon-6 with glucose and gentiobiose residues linked through β-(1 → 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. •Obesity promotes high tumor development and an intense cancer cachexia syndrome.•Walker-256 tumor-bearing obese rats present insulin resistance and macrocytic anemia.•Botryosphaeran reduced tumor development and the cachexia syndrome in obese rats.•Botryosphaeran improved metabolic and hematologic profiles of obese rats with tumor.•Botryosphaeran increased the FOXO3a activity in tumor tissue.