title: Homodimers of Vanillin and Apocynin Decrease the Metastatic Potential of Human Cancer Cells by Inhibiting the FAK/PI3K/Akt Signaling Pathway.
abstract: The spread of cancer cells to distant organs, in a process called metastasis, is the main factor that contributes to most death in cancer patients. Vanillin, the vanilla flavoring agent, has been shown to suppress metastasis in a mouse model. Here, we evaluated the antimetastatic potential of the food additive divanillin, the homodimer of vanillin, and their structurally related compounds, apocynin and diapocynin, in hepatocellular carcinoma cells. The Transwell invasion assay showed that the dimeric forms exhibited a potency higher than those of vanillin and apocynin in inhibiting invasion, with IC50values of 23.3 ± 7.4 to 41.3 ± 4.2 μM for the dimers, which are 26-34-fold lower than IC50values of vanillin and apocynin (p < 0.05). Both monomeric and dimeric forms target regulation of the invasion process by inhibiting phosphorylation of FAK and Akt. Molecular docking studies suggested that the dimers should bind more tightly than vanillin and apocynin to the Y397 pocket of the FAK FERM domain. Thus, the food additive divanillin has antimetastatic potential greater than that of the flavoring agent vanillin.
authors.affiliation: Chulabhorn Graduate Institute , Bangkok 10210, Thailand.|Center of Excellence on Environmental Health and Toxicology (EHT), Ministry of Education , Bangkok 10400, Thailand.
authors.forename: Phatcharida
authors.initials: P
authors.lastname: Jantaree
authors.affiliation: Center of Excellence on Environmental Health and Toxicology (EHT), Ministry of Education , Bangkok 10400, Thailand.
authors.forename: Kriengsak
authors.identifier: http://orcid.org/0000-0001-5858-5433
authors.initials: K
authors.lastname: Lirdprapamongkol
authors.affiliation: Chulabhorn Graduate Institute , Bangkok 10210, Thailand.|Center of Excellence on Environmental Health and Toxicology (EHT), Ministry of Education , Bangkok 10400, Thailand.
authors.forename: Wilailak
authors.initials: W
authors.lastname: Kaewsri
authors.affiliation: Chulabhorn Graduate Institute , Bangkok 10210, Thailand.
authors.forename: Charnsak
authors.initials: C
authors.lastname: Thongsornkleeb
authors.affiliation: Department of Biochemistry, Faculty of Science, Kasetsart University , Bangkok 10903, Thailand.
authors.forename: Kiattawee
authors.initials: K
authors.lastname: Choowongkomon
authors.forename: Korakot
authors.initials: K
authors.lastname: Atjanasuppat
authors.affiliation: Chulabhorn Graduate Institute , Bangkok 10210, Thailand.|Center of Excellence on Environmental Health and Toxicology (EHT), Ministry of Education , Bangkok 10400, Thailand.
authors.forename: Somsak
authors.initials: S
authors.lastname: Ruchirawat
authors.affiliation: Chulabhorn Graduate Institute , Bangkok 10210, Thailand.
authors.forename: Jisnuson
authors.identifier: http://orcid.org/0000-0002-2217-4517
authors.initials: J
authors.lastname: Svasti
mesh_terms: D000098:Acetophenones / Q000737:chemistry / Q000494:pharmacology*; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D019281:Dimerization; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D062105:Molecular Docking Simulation; D009362:Neoplasm Metastasis / Q000503:physiopathology / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000098:Acetophenones; D001547:Benzaldehydes; C056165:acetovanillone; C100058:vanillin; D019869:Phosphatidylinositol 3-Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: antimetastatic; apocynin; focal adhesion kinase; food additive; vanillin