Vanillin suppresses metastatic potential of human cancer cells through PI3K inhibition and decreases angiogenesis in vivo.
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.
Lirdprapamongkol
Kriengsak
K
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Kramb
Jan-Peter
JP
Suthiphongchai
Tuangporn
T
Surarit
Rudee
R
Srisomsap
Chantragan
C
Dannhardt
Gerd
G
Svasti
Jisnuson
J
D000098:Acetophenones / Q000494:pharmacology; D000230:Adenocarcinoma; D001547:Benzaldehydes / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects
D000098:Acetophenones; D001547:Benzaldehydes; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017228:Hepatocyte Growth Factor; C056165:acetovanillone; C100058:vanillin