A New Herbal Formula, KSG-002, Suppresses Breast Cancer Growth and Metastasis by Targeting NF- κ B-Dependent TNF α Production in Macrophages.

Sang-Mi Woo,Sunju Park,Sung-Gook Cho,Youn Kyung Choi,Seong-Gyu Ko

doi:10.1155/2013/728258

A New Herbal Formula, KSG-002, Suppresses Breast Cancer Growth and Metastasis by Targeting NF- κ B-Dependent TNF α Production in Macrophages.

Sang-Mi Woo, Sunju Park + Show 3 more

Open Access

https://doi.org/10.1155/2013/728258

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Abstract

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 (TNFα) production by inhibiting NF-κB pathway. Furthermore, a combinatorial treatment of KSG-002 with TNFα 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-κB-mediated TNFα production in macrophages.

Highlights

Tumor microenvironment is highly heterogeneous and dynamic in cell-to-cell communications, regulating tumor progression and metastases [1,2,3,4]
We developed new herbal formulae, KSG001 and KSG-002, and identified that KSG-002 but not KSG001 inhibits breast cancer growth, angiogenesis, and pulmonary metastasis by targeting tumor-associated macrophages (TAMs)
To investigate effects of KSGs on breast tumor growth and metastases in vivo, nude mice were subcutaneously injected with highly metastatic MDA-MB231 cells, when tumor volume reached about 50 mm3, orally administrated with KSG-001 (500 mg/kg/d) or KSG-002 (500 mg/kg/d)

Summary

Introduction

Tumor microenvironment is highly heterogeneous and dynamic in cell-to-cell communications, regulating tumor progression and metastases [1,2,3,4]. Tumor-associated macrophages (TAMs) are known to regulate cancer growth and metastases through alterations of tumor cell proliferation, migration, invasion, angiogenesis, immunosuppression, and extracellular matrix alteration [1, 5,6,7,8,9]. TAMs can be one of cancer therapeutic targets. TNF-alpha (TNFα) has “yin and yang” roles in cancer development and metastases [10,11,12]. TNFα released from macrophages induces cancer cell proliferation and migration [13, 14].

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