Vanillin Suppresses Metastatic Potential of Human Cancer Cells through PI3K Inhibition and Decreases Angiogenesis in Vivo

• Published in: Journal of agricultural and food chemistry Vol. 57; no. 8; pp. 3055 - 3063
• Main Authors: Lirdprapamongkol, Kriengsak, Kramb, Jan-Peter, Suthiphongchai, Tuangporn, Surarit, Rudee, Srisomsap, Chantragan, Dannhardt, Gerd, Svasti, Jisnuson
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 22.04.2009
• Subjects: Acetophenones - pharmacology; Adenocarcinoma; angiogenesis; anticarcinogenic activity; apocynin; Benzaldehydes - pharmacology; Bioactive Constituents; Biological and medical sciences; Cell Line, Tumor; cell migration; Cell Movement - drug effects; enzyme inhibition; Enzyme Inhibitors - pharmacology; Food industries; Fundamental and applied biological sciences. Psychology; Hepatocyte Growth Factor - pharmacology; human cell lines; Humans; kinases; Lung Neoplasms; Neoplasm Metastasis - prevention & control; Neovascularization, Pathologic - prevention & control; phenols; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; phosphoinositide 3-kinase; Signal Transduction - drug effects; vanillin; PI3K; signal transduction; cell migration; Vanillin; apocynin; antimetastatic; antiangiogenesis; Human; Migration; Malignant tumor; In vivo; Signal transduction; Decrease; Inhibition; Cell; Cancer
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf803366f

Vanillin, a food flavoring agent, has been shown to suppress cancer cell migration and metastasis in a mouse model, but its mechanism of action is unknown. In this report, we have examined the antimetastatic potential of vanillin and its structurally related compounds, vanillic acid, vanillyl alcohol, and apocynin on hepatocyte growth factor (HGF)-induced migration of human lung cancer cells by the Transwell assay. Vanillin and apocynin could inhibit cell migration, and both compounds selectively inhibited Akt phosphorylation of HGF signaling, without affecting phosphorylation of Met and Erk. Vanillin and apocynin could inhibit the enzymatic activity of phosphoinositide 3-kinase (PI3K), as revealed by an in vitro lipid kinase assay, suggesting that inhibition of PI3K activity was a mechanism underlying the inhibitory effect on cancer cell migration, and the presence of an aldehyde or ketone group in the vanillin structure was important for this inhibition. Vanillin and apocynin also inhibited angiogenesis, determined by the chick chorioallantoic membrane assay.