title: Saussurea lappa Clarke-Derived Costunolide Prevents TNF α -Induced Breast Cancer Cell Migration and Invasion by Inhibiting NF- κ B Activity.
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.
authors.affiliation: Laboratory of Clinical Biology and Pharmacogenomics, Center for Clinical Research and Genomics, Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Seoul 130-701, Republic of Korea.
authors.forename: Youn Kyung
authors.initials: YK
authors.lastname: Choi
authors.forename: Sung-Gook
authors.initials: SG
authors.lastname: Cho
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Woo
authors.forename: Yee Jin
authors.initials: YJ
authors.lastname: Yun
authors.forename: Jeakyung
authors.initials: J
authors.lastname: Jo
authors.forename: Wooyoung
authors.initials: W
authors.lastname: Kim
authors.forename: Yong Cheol
authors.initials: YC
authors.lastname: Shin
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Ko