Dibutyltin(IV) and Tributyltin(IV) Derivatives of meso-Tetra(4-sulfonatophenyl)porphine Inhibit the Growth and the Migration of Human Melanoma Cells

Abstract

Melanoma is the most aggressive and deadly form of skin cancer, which is largely due to its propensity to metastasize. Therefore, with the aim to inhibit the growth and the metastatic dissemination of melanoma cells and to provide a novel treatment option, we studied the effects of the melanoma treatment with two organotin(IV) complexes of the meso-tetra(4-sulfonato-phenyl)porphine, namely (Bu ₂Sn) ₂TPPS and (Bu ₃Sn) ₄TPPS. In particular, we showed that nanomolar concentrations of (Bu ₂Sn) ₂TPPS and (Bu ₃Sn) ₄TPPS are sufficient to inhibit melanoma cell growth, to increase the expression of the full-length poly (ADP-ribose) polymerase (PARP-1), to induce the cell cycle arrest respectively at G2/M and G0/G1 through the inhibition of the Cyclin D1 expression and to inhibit cell colony formation. Nanomolar concentrations of (Bu ₂Sn) ₂TPPS and (Bu ₃Sn) ₄TPPS are also sufficient to inhibit the melanoma cell migration and the expression of some adhesion receptors. Moreover, we report that (Bu ₂Sn) ₂TPPS and (Bu ₃Sn) ₄TPPS act downstream of BRAF, mainly bypassing its functions, but targeting the STAT3 signalling protein. Finally, these results suggest that (Bu ₂Sn) ₂TPPS and (Bu ₃Sn) ₄TPPS may be effective therapeutic strategies for their role in the inhibition of melanoma growth and migration.