Inhibition of angiogenesis and promotion of melanoma dormancy by vitamin E succinate.
BACKGROUND
Relapse of melanoma after surgical treatment remains a significant clinical problem in need of novel therapies. Vitamin E succinate (VES) is a promising antitumor micronutrient. We evaluated the effect of VES on melanoma dormancy and angiogenesis.


METHODS
B16F10 melanoma cells were allografted in mice. The effect of VES on melanoma dormancy was measured by monitoring tumor volume. Tumor vascularity was quantitated with CD31 immunostaining. The expression of vascular endothelial growth factor (VEGF), VEGF receptor 1, and VEGF receptor 2 in tumors was assessed by the intensity of immunostaining. VES effect on secreted VEGF protein and VEGF promoter activity was measured with enzyme-linked immunosorbent assay and transient transfection assay, respectively. Significance was determined by analysis of variance.


RESULTS
VES promoted melanoma dormancy (P =.0019) and inhibited melanoma angiogenesis (P <.0001). VES also significantly suppressed the expression of VEGF, VEGF receptor 1, and VEGF receptor 2 in melanoma tumors (P <.0001). Melanoma VEGF secretion (P =.0077) and melanoma VEGF promoter activity (P <.05) were significantly inhibited by VES.


CONCLUSIONS
VES promotes melanoma dormancy and inhibits melanoma angiogenesis. The mechanism of the VES antiangiogenesis effect involves the inhibition of VEGF gene transcription. These findings support future studies of VES in the prevention of melanoma metastasis.
Malafa
Mokenge P
MP
Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA. mmalafa@moffitt.usf.edu
Fokum
Frida D
FD
Smith
LaKesha
L
Louis
Audreen
A
D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016228:Endothelial Growth Factors; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D024505:Tocopherols; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014810:Vitamin E; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D024505:Tocopherols