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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 TNF α -induced NF- κ B 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  TNF α -induced invasion and migration of MDA-MB-231 cells. Costunolide further suppressed TNF α -induced NF- κ B signaling activation, resulting in a reduced expression of MMP-9, a well-known NF- κ B-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 TNF α -induced NF- κ B activation, suggesting that costunolide as well as SLC may be promising anticancer drugs, especially for metastatic breast cancer.

evidence-based complementary and alternative medicine

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