Lau,CBS (reprint author),Chinese Univ Hong Kong,Inst Chinese Med,Shatin,Hong Kong,Peoples R China.
Cyclopeptide RA-V has potent anti-tumor and anti-angiogenic activities, but its potential anti-metastatic activity is unknown. Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM), allowing them to migrate to adjacent tissues and ultimately metastasize. Hence, the present study aimed to investigate the effects of RA-V on cell adhesion, migration, invasion and matrix degradation, and its underlying mechanism in two human breast cancer cell lines MCF-7 (ER-positive) and MDA-MB-231 (ER-negative). Our results demonstrated that RA-V (12.5 nM) can significantly inhibit breast cancer cell adhesion and migration via interfering cofilin signaling and chemokine receptors involved in cell migration. RA-V reduced the expressions of vascular intracellular adhesion molecule (VCAM), intracellular adhesion molecule (ICAM), focal adhesion kinase (FAR) and integrins. The activities and expressions of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) and urokinase-type of plasminogen activator (uPA) were also inhibited by RA-V. Furthermore, RA-V inhibits the expressions of EGFR, PI3K/AKT and NF-kappa B signaling molecules, and reduces the binding of beta-estradiol to ER via affecting binding ability of ER in MCF-7 cells. RA-V inhibits breast cancer cell migration, adhesion and ECM degradation in vitro, implying that RA-V is a potential anti-metastatic agent in breast cancer, and likely acts via PI3K/AKT and NF-kappa B signaling pathways in both ER-positive and ER-negative breast cancer cells. (C) 2015 Elsevier B.V. All rights reserved.
National Natural Science Foundation of China [U1032602, 91013002, 30725048]
; Foundation of Chinese Academy of Sciences (Hundred Talents Program) [XDA09030301-4]
; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK) from Hong Kong Special Administrative Region
; Chinese University of Hong Kong (FIS-A) 
1.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Ch, Kunming Inst Bot, Kunming 650201, Yunnan, Peoples R China 2.Chinese Univ Hong Kong, Inst Chinese Med, Shatin, Hong Kong, Peoples R China 3.Chinese Univ Hong Kong, State Key Lab Phytochem & Plant Resources West Ch, Shatin, Hong Kong, Peoples R China 4.Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China