title: Protocatechuic acid inhibits lung cancer cells by modulating FAK, MAPK, and NF-κB pathways.
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.
authors.affiliation: a Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung City, Taiwan and Institute of Microbiology and Immunology , Chung Shan Medical University , Taichung City , Taiwan.
authors.forename: Shih-ming
authors.initials: SM
authors.lastname: Tsao
authors.forename: Te-chun
authors.initials: TC
authors.lastname: Hsia
authors.forename: Mei-chin
authors.initials: MC
authors.lastname: Yin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C508606:CXCL8 protein, human; D005353:Fibronectins; D062385:Hydroxybenzoates; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; C009091:protocatechuic acid; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9