Anticancer effects of carboxymethylated (1→3)(1→6)-ß-D-glucan (botryosphaeran) on multicellular tumor spheroids of MCF-7 cells as a model of breast cancer.

Breast cancer is the most common cancer worldwide among the female population. The fungal exopolysaccharide botryosphaeran is a (1→3)(1→6)-ß-D-glucan with limited solubility in water that can be promoted through carboxymethylation. Thus, the aim of this study was to examine in-vitro anticancer effects of carboxymethylated-botryosphaeran (CM-BOT) on breast cancer MCF-7 cells cultivated in multicellular tumor spheroids (MCTS). CM-BOT (≥ 600 µ/ml) decreased the viability (resazurin assay) of MCF-7 grown in monolayers after 24 hr incubation. Although CM-BOT did not markedly alter viability of MCTS in the resazurin assay after 24, 48 or 72 hr, CM-BOT ≥ 600 µg/ml produced cell-death by apoptosis after 72 hr utilizing the triple staining assay and labeling dead cells with propidium iodide, which can also be visualized on the architecture of MCTS. CM-BOT (1000 µg/ml) inhibited cell proliferation, which resulted in MCTSs with smaller diameters than controls. CM-BOT at all concentrations examined decreased the ability of MCF-7 to form colonies and to migrate in the extracellular matrix. This is the first report using MCTS-architecture to study anti-tumor effects of ß-glucans. Our findings are important in the search for compounds for use in breast cancer therapy, or as adjuvants in reducing the adverse effects of mammary tumor chemotherapy.