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.