Soyasapogenols contained in soybeans suppress tumour progression by regulating macrophage differentiation into the protumoural phenotype

• We found compounds isolated from soybeans that regulate macrophage differentiation.
• Soyasapogenols (SSGs) regulate macrophage differentiation by suppression of STAT3 activation.
• SSGs inhibit tumour proliferation by suppression of STAT3 activation.
• SSGs inhibit tumour progression by regulating macrophage differentiation in tumour-bearing mice.
• SSGs may represent new agents that can be used for the prevention of various malignant tumours.

Tumour-associated macrophages (TAMs) polarized to the protumoural M2 phenotype promote tumour proliferation and are considered to be a therapeutic target in patients with malignant tumours. In this study, we tried to identify natural compounds that inhibit TAM polarization into the M2 phenotype. We found that an extract of soybeans suppressed M2 polarization, and that soyasapogenols, major compounds contained in soybeans, significantly inhibited the M2 polarization and increased the secretion of IL-12 produced by M1 macrophages. Soyasapogenols suppressed the activation of STAT3 in both macrophages and tumour cells, and inhibited the proliferation of U373, SaOS2 and LM8 tumour cells. Furthermore, oral administration of soyasapogenol B significantly suppressed both subcutaneous tumour development and lung metastasis in a LM8 tumour-bearing mice. An anti-tumour immune response was also induced by the administration of soyasapogenol B. Therefore, soyasapogenols may represent new agents that can be used for the prevention and/or treatment of various malignant tumours.