Effect of Amentoflavone on the Inhibition of Pulmonary Metastasis Induced by B16F-10 Melanoma Cells in C57BL/6 Mice

This study was an investigation of the antimetastatic activity of amentoflavone using B16F-10 melanoma—induced experimental lung metastasis in C57BL/6 mice. Amentoflavone treatment significantly reduced tumor nodule formation accompanied by reduced lung collagen hydroxyproline, hexosamine, and uronic acid levels. Serum sialic acid and γglutamyl transpeptidase levels were also significantly inhibited after amentoflavone treatment. Amentoflavone treatment up-regulated the lung tissue inhibitor of metalloprotease-1 and tissue inhibitor of metalloprotease-2 expression. The cytokine profile and growth factors such as interleukin-1β , interleukin-6, tumor necrosis factor-α, granulocyte monocyte— colony stimulating factor, vascular endothelial growth factor, interleukin-2, and tissue inhibitor of metalloprotease-1 in the serum of these animals were markedly altered after amentoflavone treatment. This altered level of cytokines after amentoflavone treatment was also accompanied by enhanced natural killer cell antibody—dependent cellular cytotoxicity. The study reveals that amentoflavone treatment could alter proinflammatory cytokine production and could inhibit the activation and nuclear translocation of p65, p50, c-Rel subunits of nuclear factor—κB, and other transcription factors such as c-fos, activated transcription factor—2, and cyclic adenosine monophosphate response element—binding protein in B16F-10 melanoma cells.