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Tumor-associated macrophages (TAMs) in tumor microenvironment regulate cancer progression and metastases. In breast cancer, macrophage infiltration is correlated with a poor prognosis. While metastatic breast cancer is poor prognostic with a severe mortality, therapeutic options are still limited. In this study, we demonstrate that KSG-002, a new herbal composition of radices  Astragalus membranaceus  and  Angelica gigas , suppresses breast cancer via inhibiting TAM recruitment. KSG-002, an extract of radices  Astragalus membranaceus  and  Angelica gigas  at 3 : 1 ratio, respectively, inhibited MDA-MB-231 xenograft tumor growth and pulmonary metastasis in nude mice, while KSG-001, another composition (1 : 1 ratio,  w/w ), enhanced tumor growth, angiogenesis, and pulmonary metastasis,  in vivo . KSG-002 further decreased the infiltrated macrophage numbers in xenograft tumor cohorts. In Raw264.7 cells, KSG-002 but not KSG-001 inhibited cell proliferation and migration and reduced TNF-alpha (TNF  α  ) production by inhibiting NF-  κ  B pathway. Furthermore, a combinatorial treatment of KSG-002 with TNF  α   inhibited a proliferation and migration of both MDA-MB-231 and Raw264.7 cells. Taken together, we conclude that KSG-002 suppresses breast cancer growth and metastasis through targeting NF-  κ  B-mediated TNF  α   production in macrophages.

evidence-based complementary and alternative medicine

A New Herbal Formula, KSG-002, Suppresses Breast Cancer Growth and Metastasis by Targeting NF-κB-Dependent TNFαProduction in Macrophages