Protocatechuic acid inhibits lung cancer cells by modulating FAK, MAPK, and NF-κB pathways

Nutr Cancer. 2014;66(8):1331-41. doi: 10.1080/01635581.2014.956259. Epub 2014 Oct 30.

Abstract

Cytotoxic effects of protocatechuic acid (PCA) upon 3 nonsmall cell lung cancer (NSCLC) cell lines, A549, H3255, and Calu-6 cell lines, were examined. PCA at 1, 2, 4, and 8 μM was used to treat these cells. Results showed that PCA dose-dependently reduced cell growth; and at 2-8 μM enhanced protein expression of Bax and cleaved caspase-3; as well as diminished Bcl-2 expression. This compound destabilized mitochondrial membrane via increasing caspase-3 activity, decreasing mitochondrial membrane potential and Na(+)-K(+)-ATPase activity in these cells. PCA treatments dose-dependently decreased protein expression of vascular endothelial growth factor and fibronectin, as well as lowered interleukin (IL)-6 and IL-8 release; and at 2-8 μM suppressed protein expression of basic fibroblast growth factor, matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, PCA treatments dose-dependently downregulated nuclear factor kappa (NF-κ)B p50 and NF-κB p65 protein expression, and at 2-8 μM suppressed protein expression of p-p38, p-JNK, and p-focal adhesion kinase (FAK). Our data revealed that PCA declined FAK, mitogen-activated protein kinase, and NF-κB activation, which subsequently decreased the production of cytokines and growth factors, and consequently inhibited proliferation of 3 test NSCLC cells. These findings suggest that PCA could provide wide-ranging anti-NSCLC potency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Focal Adhesion Protein-Tyrosine Kinases / genetics
  • Focal Adhesion Protein-Tyrosine Kinases / metabolism*
  • Humans
  • Hydroxybenzoates / pharmacology*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Signal Transduction
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • CXCL8 protein, human
  • Fibronectins
  • Hydroxybenzoates
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • bcl-2-Associated X Protein
  • protocatechuic acid
  • Focal Adhesion Protein-Tyrosine Kinases
  • Mitogen-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9