To assess the inhibitory effects of
methylselenol on the invasion of murine B16F10
melanoma cells, we carried out in vivo and in vitro experiments using
Se-methylselenocysteine (Se-MSC) and
selenomethionine (SeMet), respectively. In an animal experiment, the supplementation of
drinking water with Se-MSC (4 ppm Se) led to a significant increase in Se levels in the lung, liver and serum in mice. Mice given a mash diet or water supplemented with Se-MSC (2, 4 and 6 ppm Se in the mash diet, and 2 and 4 ppm Se in the
drinking water) displayed an almost completely diminished pulmonary
metastasis of B16F10
melanoma cells and an enhanced survival, compared to the control mice which were given a basal diet. Treatment with non-cytotoxic concentrations of SeMet (2.5, 5 and 10 microM plus 0.02 U/ml METase,
methioninase) induced a substantial decrease in the expression of
integrin alphavbeta3, the FN receptor and adhesion ability to
vitronectin (VN) and
fibronectin (FN) in B16F10
melanoma cells. Moreover, these compounds suppressed
gelatinase activity, invasive ability and
wound migration in the culture system. SeMet-METase prevented the conversion of pro-MMP-9 to its active form and decreased
pro-MMP-2 activities in a zymogram. The pre-treatment of B16F10
melanoma cells with SeMet-METase led to a decrease in pulmonary
metastasis and extended survival in mice injected with
tumor cells. Collectively, our results indicate that
integrin expression is crucial in promoting the metastatic phenotype in murine B16F10
melanoma cells by supporting specific adhesive and invasive properties, suggesting that Se-MSC effectively reduces the
metastasis of B16F10
melanoma cells as a nutritional adjuvant.
Methylselenol may also contribute to the suppression of
integrin expression.