title: Cyclopeptide RA-V inhibits cell adhesion and invasion in both estrogen receptor positive and negative breast cancer cells via PI3K/AKT and NF-κB signaling pathways.
abstract: 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 (FAK) 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-κB signaling molecules, and reduces the binding of β-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-κB signaling pathways in both ER-positive and ER-negative breast cancer cells.
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Hoi-Wing
authors.initials: HW
authors.lastname: Leung
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Grace Gar-Lee
authors.initials: GG
authors.lastname: Yue
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Si-Meng
authors.initials: SM
authors.lastname: Zhao
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Julia Kin-Ming
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Kwok-Pui
authors.initials: KP
authors.lastname: Fung
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
authors.forename: Ping-Chung
authors.initials: PC
authors.lastname: Leung
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Electronic address: claralau@cuhk.edu.hk.
authors.forename: Clara Bik-San
authors.initials: CB
authors.lastname: Lau
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China. Electronic address: nhtan@mail.kib.ac.cn.
authors.forename: Ning-Hua
authors.initials: NH
authors.lastname: Tan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D010456:Peptides, Cyclic; D011960:Receptors, Estrogen; C043547:RA V; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
keywords: Breast cancer; Cell adhesion; Cell invasion; Cyclopeptide; Metastasis