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: Hoi-Wing Leung, Zhe Wang, Grace Gar-Lee Yue, Si-Meng Zhao, Julia Kin-Ming Lee, Kwok-Pui Fung, Ping-Chung Leung, Clara Bik-San Lau, Ning-Hua Tan
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1853 Issue 8 Pg. 1827-40 (Aug 2015) ISSN: 0006-3002 [Print] Netherlands
• PMID: 25953046 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• NF-kappa B
• Peptides, Cyclic
• Receptors, Estrogen
• RA V
• Phosphatidylinositol 3-Kinases
• Oncogene Protein v-akt

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Female
• HeLa Cells
• Humans
• MCF-7 Cells
• NF-kappa B (metabolism)
• Neoplasm Invasiveness
• Oncogene Protein v-akt (metabolism)
• Peptides, Cyclic (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Receptors, Estrogen (genetics, metabolism)
• Signal Transduction (drug effects)