Antiproliferative activity of vanadium compounds: effects on the major malignant melanoma molecular pathways.

摘要: Malignant melanoma (MM) is the most fatal skin cancer, whose incidence has critically increased in last decades. Recent molecular therapies are giving excellent results remission of but often they induce drug resistance patients limiting their therapeutic efficacy. The search for new compounds able to overcome therefore essential. Vanadium recently been cited its anticancer properties against several tumors, only a few data regard effect MM. In previous work we demonstrated activity four different vanadium species towards MM cell lines. inorganic anion vanadate(v) (VN) and oxidovanadium(iv) complex [VO(dhp)2] (VS2), where dhp 1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate, showed IC50 values 4.7 2.6 μM, respectively, A375 line, causing apoptosis cycle arrest. Here demonstrate involvement Reactive Oxygen Species (ROS) production pro-apoptotic these two V evaluate activation regulators, investigate mechanisms involved antitumor activity. We establish that VN VS2 treatments reduce phosphorylation extracellular-signal regulated kinase (ERK) by about 80%, deactivation mitogen activated protein (MAPK) pathway cells. also dephosphorylation retinoblastoma (Rb) (VN 100% 90%), together with pronounced increase cyclin-dependent inhibitor 1 p21 (p21Cip1) expression up 1800%. Taken together, our confirm cells, highlighting ability through generation ROS arrest counteracting MAPK strongly inducing p21Cip1 Rb hypo-phosphorylation.