Synergistic effect of diosmin and interferon-alpha 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.
Alvarez
Nuria
N
University of Murcia Institute of Research into Aging, Department of Pathology, Faculty of Medicine, University of Murcia, Murcia, Spain. nalvarez@um.es
Vicente
Vicente
V
Martínez
Cristina
C
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004145:Diosmin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D005260:Female; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D011994:Recombinant Proteins
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004145:Diosmin