Melanoma is a solid tumor that is notoriously resistant to chemotherapy, and its incidence is rapidly increasing. Recently, several signaling pathways have been demonstrated to contribute to melanoma tumorigenesis, including constitutive activation of MAP kinase, Akt and stat-3. The activation of multiple pathways may account in part for the difficulty in treatment of melanoma. In a recent screen of compounds, we found that an organopalladium complex showed significant antiproliferative activity against melanoma cells. This complex, tris(dibenzylideneacetone) dipalladium (Tris DBA), has activity against Bl 6 murine and A375 human melanoma in vivo. Tris DBA inhibits several signaling pathways including activation of MAP kinase, Akt, stat-3 and S6 kinase activation. Tris (dibenzylideneacetone)dipalladium is thus a novel compound that is a member of a class of noble metal complexes with potential antitumor activity. Further preclinical evaluation of TrisDBA and related complexes is warranted.
