Inhibition of the growth and the migration of human melanoma cells at nanomolar concentrations of dibutyltin(IV) and tributyltin(IV) derivatives of the meso-tetra(4-sulfonatophenyl)porphine.

Melanoma is responsible worldwide for most of the skin cancer related deaths; which is largely due to its propensity to metastasize1. Therefore, the aim of our work was to understand the consequences on cellular growth and migration of the treatment with nanomolar concentrations of two organotin(IV) complexes of the meso-tetra(4-sulfonato-phenyl)porphine, the (Bu2Sn)2TPPS and the (Bu3Sn)4TPPS. Recently, we already reported that (Bu3Sn)4TPPS and (Bu2Sn)2TPPS induce apoptosis in A375 human melanoma cells.2-4 In this work, we showed that nanomolar concentration of (Bu2Sn)2TPPS and (Bu3Sn)4TPPS are sufficient to inhibit melanoma cell growth, to increase the expression of BRAF signalling proteins, 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. Notably, nanomolar concentrations of (Bu2Sn)2TPPS and (Bu3Sn)4TPPS are also sufficient to inhibit the melanoma cell migration, to decreases the expression of FAK, and STAT3 signalling protein, Integrin and CAM adhesion receptors. Interestingly, the (Bu2Sn)2TPPS and the (Bu3Sn)4TPPS act downstream of BRAF mainly bypassing its functions but targeting STAT3 signalling protein. Therefore, the results obtained suggest that the (Bu2Sn)2TPPS and the (Bu3Sn)4TPPS could be potential chemotherapeutic agents for their role in the inhibition of melanoma growth and migration.