4.6 Article

VI-14, a novel flavonoid derivative, inhibits migration and invasion of human breast cancer cells

Journal

TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 261, Issue 2, Pages 217-226

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2012.04.011

Keywords

VI-14; MMP-2/9; MAPK; NF-kappa B; Invasion

Funding

  1. State Key Laboratory of Natural Medicines, China Pharmaceutical University [JKGZ201101]
  2. National Natural Science Foundation of China [30701032, 21072232]
  3. Natural Science Foundation of Jiangsu Province [BK2010432, BK2011620]
  4. National Science & Technology Major Project [2012ZX09304-001]
  5. Program for Changjiang Scholars and Innovative Research Team in University [PCSIRT-IRT1193]

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It has been well characterized that flavonoids possess pronounced anticancer potentials including anti-angiogenesis, anti-metastasis, and pro-apoptosis. Herein, we report, for the first time, that VI-14, a novel flavonoid derivative, possesses anti-cancer properties. The purpose of this study is to investigate the anti-migration and anti-invasion activities of VI-14 in breast cancer cells. Our data indicate that VI-14 inhibits adhesion, migration and invasion of MDA-MB-231 and MDA-MB-435 human breast cancer cells. MDA-MB-231 cells treated with VI-14 display reduced activities and expressions of ECM degradation-associated proteins including matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) at both the protein and mRNA levels. Meanwhile, VI-14 treatment induces an up-regulated expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and 2 (TIMP-2) in MDA-MB-231 cells. Westem blotting results show that phosphorylation levels of critical components of the MAPK signaling pathway, including ERK, JNK and P38, are dramatically decreased in VI-14-treated MDA-MB-231 cells. Furthermore, treatment of VI-14 significantly decreases the nuclear levels and the binding ability of nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1). Taken together, our data suggest that VI-14 treatment suppresses migration and motility of breast cancer cells, and VI-14 may be a potential compound for cancer therapy. (C) 2012 Elsevier Inc. All rights reserved.

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