Decavanadate Compound Displays In Vitro and In Vivo Antitumor Effect on Melanoma Models.

Abstract

The efficacy of available treatments for melanoma is limited by side effects and the rapidly emerging resistance to treatment. In this context, the decavanadate compounds represent promising tools to design efficient therapeutic agents. In our study, we synthesized a dimagnesium disodium decavanadate icosahydrate compound (Mg₂Na₂V₁₀O₂₈·20H₂O) and investigated its structure stability as well as its antimelanoma effects. Results showed that the Mg₂Na₂V₁₀O₂₈·20H₂O compound is structured in a monoclinic system with the space group C2/c, stabilized by oxygen vertices, hydrogen bonds, and van der Waals interactions. Interestingly, we found that this newly synthesized compound reduced the viability of human (IGR39, IGR37, and SKMEL28) and murine (B16-F10) melanoma cells in a dose-dependent manner. The IC₅₀ values ranged from 7.3 to 18 μM after 24 h and decreased to 1.4 μM after 72 h of treatment. Notably, this effect was more important than that of cisplatin (IC₅₀ = 3 μM after 72 h of treatment), a chemotherapeutic agent, commonly used in the treatment of malignant melanoma. Furthermore, the cytotoxicity of the decavanadate compound was relatively weak on normal human keratinocytes (HaCaT), with a light effect (IC₅₀ >> 70 μM) observed after 24 h of treatment. Thus, the Mg₂Na₂V₁₀O₂₈·20H₂O compound displayed an advantage over cisplatin, which was reported to be much more aggressive to the keratinocyte cell line (IC₅₀ = 23.9 μM). Moreover, it inhibited dose-dependently the adhesion of IGR39 cells to collagen (IC₅₀ = 2.67 μM) and fibronectin, as well as their migration with an IC₅₀ value of 2.23 μM. More interestingly, its in vivo administration to B16-F10 allografted mice, at the nontoxic dose of 50 μg (2.5 mg/kg), prevented and suppressed by 70% the tumor growth, compared to the nontreated mice. Moreover, this compound has also allowed a recovery against inflammation induced in mice by a mixture of DMBA and croton oil. Thus, all our results showed the potential of the Mg₂Na₂V₁₀O₂₈·20H₂O compound to prevent and efficiently treat the growth and metastasis of melanoma.