Nitidine Chloride inhibits breast cancer cells migration and invasion by suppressing c-Src/FAK associated signaling pathway

Cancer Lett. 2011 Dec 27;313(2):181-91. doi: 10.1016/j.canlet.2011.09.001. Epub 2011 Sep 10.

Abstract

Nitidine is a benzophenanthridine alkaloid, which has been shown to have anti-tumor properties. Here, we demonstrated that Nitidine Chloride (NC) could inhibit breast cancer cells migration and invasion both in vitro and in vivo. Meanwhile, the protrusion formation and partial proteolytic activity of MMP-9 and MMP-2 were attenuated by NC in a dose-dependent manner in MDA-MB-231 cells. Furthermore, addition NC to cells significantly decreases PDGF induced phosphorylation of c-Src, FAK, MAPKs, activation of RhoA, Rac1 and AP-1 transcriptional activity. Taken together, our results indicate that NC could have potential as a novel anti-metastasis drug to breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Benzophenanthridines / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • CSK Tyrosine-Protein Kinase
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Focal Adhesion Kinase 1 / metabolism
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Platelet-Derived Growth Factor / toxicity
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • rac1 GTP-Binding Protein / metabolism
  • rhoA GTP-Binding Protein / metabolism
  • src-Family Kinases

Substances

  • Antineoplastic Agents, Phytogenic
  • Benzophenanthridines
  • Platelet-Derived Growth Factor
  • RAC1 protein, human
  • Transcription Factor AP-1
  • nitidine
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • src-Family Kinases
  • CSK protein, human
  • Extracellular Signal-Regulated MAP Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • rac1 GTP-Binding Protein
  • rhoA GTP-Binding Protein