Synergistic Effect of Diosmin and Interferon-α on Metastatic Pulmonary Melanoma

Melanoma is the most important skin cancer in terms of mortality, besides developing metastasis in about a third of the patients. Interferon-alpha (IFN-alpha), a highly toxic cytokine, tends to be one of the most important treatments for melanoma. Much effort is being directed at obtaining less-toxic antitumoral compounds, particularly natural compounds such as flavonoids. Our aim was to study the combined treatment of metastatic lung melanoma with IFN-alpha and diosmin in a murine model. In this article, we report the effect of a combined treatment of IFN-alpha and the flavonoid, diosmin, on a murine model of metastatic B16F10 melanoma, assessed both macroscopically (counting subpleural nodules) and microscopically by image analysis (calculating three indices). IFN-alpha showed a dose-dependent anti-invasive and antiproliferative activity in our study, while diosmin showed an anti-invasive activity similar to the lower dose of IFN-alpha used. However, the most relevant result was the synergistic antiproliferative effect shown by the combination of the flavonoid and the lowest dose of IFN-alpha, which was similar to that produced by the highest dose of the cytokine alone.