Development of new therapeutic strategies for regulating macrophage activation by natural compounds

在疾病环境中，巨噬细胞被不同程度地激活。例如，M1激活的巨噬细胞参与肥胖和动脉粥样硬化，而M2激活的肿瘤相关巨噬细胞促进肿瘤进展。为了开发新的治疗策略，我们通过筛选天然化合物的文库，鉴定了几种调节巨噬细胞M1或M2活化的化合物。其中，熊果酸和洋葱素A通过抑制STAT3活化来抑制肿瘤进展。这两种化合物在鼠肉瘤模型中显著抑制皮下肿瘤发展和肺转移。通过这些结果，应用熊果酸和洋葱素A被认为是一种潜在的新的靶向巨噬细胞活化的抗癌疗法。

Macrophages are variously activated in disease environment. For example, M1-activated macrophages are involved in obesity and atherosclerosis, whereas M2-activated tumor-associated macrophages promote tumor progression. To develop new therapeutic strategies we identified several compounds that regulate M1- or M2-activation of macrophages by screening the library of natural compounds. Among them, colosolic acid and onionin A suppressed tumor progression by means of suppressing STAT3 activation. These two compounds significantly suppressed subcutaneous tumor development and lung metastasis in a murine sarcoma model. Through these results, application of colosolic acid and onionin A is considered a potential new anticancer therapy targeting macrophage activation.