Deguelin inhibits the migration and invasion of lung cancer A549 and H460 cells via regulating actin cytoskeleton rearrangement

Int J Clin Exp Pathol. 2015 Dec 1;8(12):15582-90. eCollection 2015.

Abstract

Deguelin, the main components from Mundulea sericea, was reported to suppress the growth of various cancer cells. However, the effect of Deguelin on tumor cell invasion and metastasis and its mechanism still unclear so far. In this study, we investigated the effects of Deguelin on the cell invasion in human lung cancer A549 and H460 cells. Our results demonstrate that Deguelin can significantly inhibited cell proliferation, cell migration and cell invasion. Moreover, Deguelin could also affected reorganization of the actin cytoskeleton and decreased filopodia and lamellipodia formation. Furthermore, deguelin-treated tumors showed decreased the tumor metastasis related genes such as CD44, MMP2 and MMP9 at protein and mRNA levels and the content of CEA, SCC, NSE, CYFAR21-1. In addition, Deguelin down-regulated protein expression of Rac1 and Rock1, which are impotent in actin cytoskeleton rearrangements and cell motility. Together, our results suggest that Deguelin inhibit tumor growth and metastasis of lung cancer cells and might be a candidate compound for curing lung cancer.

Keywords: Deguelin-actin; Lung cancer; cytoskeleton; invasion; rearrangement.

MeSH terms

  • Actin Cytoskeleton / drug effects*
  • Actin Cytoskeleton / metabolism
  • Actin Cytoskeleton / pathology
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness
  • Pseudopodia / drug effects
  • Pseudopodia / metabolism
  • Rotenone / analogs & derivatives*
  • Rotenone / pharmacology
  • Signal Transduction / drug effects
  • rac1 GTP-Binding Protein / metabolism
  • rho-Associated Kinases / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • CD44 protein, human
  • Hyaluronan Receptors
  • RAC1 protein, human
  • Rotenone
  • ROCK1 protein, human
  • rho-Associated Kinases
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • rac1 GTP-Binding Protein
  • deguelin