Tumor suppressor berberine binds VASP to inhibit cell migration in basal-like breast cancer

Oncotarget. 2016 Jul 19;7(29):45849-45862. doi: 10.18632/oncotarget.9968.

Abstract

Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent.

Keywords: VASP; basal-like subtype breast cancer; berberine; polymerization.

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Berberine / pharmacology*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Adhesion Molecules / antagonists & inhibitors*
  • Cell Adhesion Molecules / biosynthesis
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Mice
  • Mice, Nude
  • Microfilament Proteins / antagonists & inhibitors*
  • Microfilament Proteins / biosynthesis
  • Phosphoproteins / antagonists & inhibitors*
  • Phosphoproteins / biosynthesis
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Cell Adhesion Molecules
  • Microfilament Proteins
  • Phosphoproteins
  • vasodilator-stimulated phosphoprotein
  • Berberine