title: Vitamin C down-regulates VEGF production in B16F10 murine melanoma cells via the suppression of p42/44 MAPK activation.
abstract: It is known that vitamin C induces apoptosis in several kinds of tumor cells, but its effect on the regulation of the angiogenic process of tumors is not completely studied. Vascular endothelial growth factor (VEGF) is the most well-known angiogenic factor, and it has a potent function as a stimulator of endothelial survival, migration, as well as vascular permeability. Therefore, we have investigated whether vitamin C can regulate the angiogenic process through the modulation of VEGF production from B16F10 melanoma cells. VEGF mRNA expression and VEGF production at protein levels were suppressed by vitamin C. In addition, we found that vitamin C suppressed the expression of cyclooxygenase (COX)-2 and that decreased VEGF production by vitamin C was also restored by the administration of prostaglandin E2 which is a product of COX-2. These results suggest that vitamin C suppresses VEGF expression via the regulation of COX-2 expression. Mitogen-activated protein kinases are generally known as key mediators in the signaling pathway for VEGF production. In the presence of vitamin C, the activation of p42/44 MAPK was completely inhibited. Taken together, our data suggest that vitamin C can down-regulate VEGF production via the modulation of COX-2 expression and that p42/44 MAPK acts as an important signaling mediator in this process.
authors.affiliation: Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ha Na
authors.initials: HN
authors.lastname: Kim
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.forename: Joo Myung
authors.initials: JM
authors.lastname: Kong
authors.forename: Seyeon
authors.initials: S
authors.lastname: Bae
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Naeun
authors.initials: N
authors.lastname: Lee
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Cho
authors.forename: Seung Koo
authors.initials: SK
authors.lastname: Lee
authors.forename: Hang-Rae
authors.initials: HR
authors.lastname: Kim
authors.forename: Young-il
authors.initials: YI
authors.lastname: Hwang
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D008546:Melanoma, Experimental; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D010766:Phosphorylation; D013449:Sulfonamides / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015232:Dinoprostone; D001205:Ascorbic Acid