Saussurea lappaClarke-Derived Costunolide Prevents TNFα-Induced Breast Cancer Cell Migration and Invasion by Inhibiting NF-κB Activity

Youn Kyung Choi,Yong Cheol Shin,Wooyoung Kim,Sung-Gook Cho,Sang-Mi Woo,Jeakyung Jo,Seong-Gyu Ko,Yee Jin Yun

doi:10.1155/2013/936257

Abstract

Saussurea lappa Clarke (SLC) has been used as a traditional medicine in Korea, China, and Japan for the treatment of abdominal pain and tenesmus. Costunolide, a sesquiterpene lactone isolated from SLC, has diverse medicinal effects. However, the anticancer effects of costunolide are still unclear in breast cancer. In this study, we demonstrate that costunolide suppresses tumor growth and metastases of MDA-MB-231 highly metastatic human breast cancer cells via inhibiting TNFα-induced NF-κB activation. Costunolide inhibited MDA-MB-231 tumor growth and metastases without affecting body weights in the in vivo mouse orthotopic tumor growth assays. In addition, costunolide inhibited in vitro TNFα-induced invasion and migration of MDA-MB-231 cells. Costunolide further suppressed TNFα-induced NF-κB signaling activation, resulting in a reduced expression of MMP-9, a well-known NF-κB-dependent gene to mediate breast cancer cell growth and metastases. Therefore, we conclude that SLC and its derivative costunolide suppress breast cancer growth and metastases by inhibiting TNFα-induced NF-κB activation, suggesting that costunolide as well as SLC may be promising anticancer drugs, especially for metastatic breast cancer.

Highlights

Most breast cancer is an epithelial tumor that develops from mammary gland tissue and the inner lining of milk ducts [1]
Because TNFα expression is abundant in tumor microenvironment, and its expression is correlated with poor prognoses [14, 15], we investigate effects of Saussurea lappa Clarke (SLC) on highly metastatic MDA-MB-231 cells
We found that Saussurea lappa Clarke-derived costunolide suppressed TNFα-induced MDA-MB-231 breast cancer cell migration and invasion by inhibiting NF-κB activity (Figure 5(c))

Summary

Introduction

Most breast cancer is an epithelial tumor that develops from mammary gland tissue and the inner lining of milk ducts [1]. Cancer metastasis is the spread of tumor cells from an original site to distant parts of the body This event consists of multistep processes, which includes tumor cell dissemination, extracellular matrix (ECM) degradation, tumor cell invasion into the ECM, angiogenesis, and secondary metastatic tumor growth [5,6,7]. Primary tumors metastasize to specific organs; for example, aggressive breast cancers selectively metastasize to lung, bone, and brain tissue. This organ tropism seems to be related to different gene expression patterns [8,9,10]. We found that SLC and costunolide inhibit TNFα-mediated breast cancer cell migration and invasion by inhibiting NF-κB activation, thereby suggesting the antimetastatic property of costunolide using highly metastatic MDA-MB-231 breast cancer cells

Materials and Methods

Results

Discussion