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VI-14, a novel flavonoid derivative, inhibits migration and invasion of human breast cancer cells
Authors:Li Fanni  Li Chenglin  Zhang Haiwei  Lu Zhijian  Li Zhiyu  You Qidong  Lu Na  Guo Qinglong
Affiliation:
  • a State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China
  • b Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, People's Republic of China
  • Abstract: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. Western 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-κB) 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.
    Keywords:MTT, 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide   MMP, matrix metalloproteinase   TIMP, tissue inhibitor of metalloproteinase   ECM, extracellular matrix   MAPK, mitogen-activated protein kinase   ERK, extracellular signal-regulated kinase   JNK, c-Jun N-terminal kinase   AP-1, activator protein-1   NF-κB, nuclear factor-kappa B
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