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
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / metabolism*
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Down-Regulation
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Fibronectins / genetics
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Fibronectins / metabolism
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Focal Adhesion Protein-Tyrosine Kinases / genetics
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Focal Adhesion Protein-Tyrosine Kinases / metabolism*
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Humans
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Hydroxybenzoates / pharmacology*
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Interleukin-8 / genetics
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Interleukin-8 / metabolism
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism*
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Signal Transduction
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
Substances
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BAX protein, human
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CXCL8 protein, human
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Fibronectins
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Hydroxybenzoates
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IL6 protein, human
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Interleukin-6
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Interleukin-8
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NF-kappa B
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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bcl-2-Associated X Protein
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protocatechuic acid
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Focal Adhesion Protein-Tyrosine Kinases
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Mitogen-Activated Protein Kinases
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CASP3 protein, human
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Caspase 3
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MMP2 protein, human
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Matrix Metalloproteinase 2
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MMP9 protein, human
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Matrix Metalloproteinase 9