(Bu3Sn)4TPPS and (Bu2Sn)2TPPS significantly inhibit the growth, migrationand tumorigenicity of human malignant melanoma cells

Abstract

Melanoma is one of the most aggressive and treatment-resistant human cancers, it is responsible worldwide for the 80% of skin cancer related deaths which is largely due to its propensity to metastasize to other organs. The growing understanding of the pathways involved in melanoma progression and development has led to the identification of some interesting new molecules, however, the treatment options for metastatic melanoma remain limited. Indeed, the key step in metastasis development is the tumour cell invasion of the nearby host tissue and the journey powerfully depends on the detachment of single tumour cells from the primary tumour. Therefore, the ability to block the migratory and invasive capacity of tumour cells offers a new approach to treating patients with malignant disease. In this contest, the aim of our work was to understand the consequences on melanoma metastatic progression and migration of the treatment with very low concentrations of two organotin(IV) complexes of the meso-tetra(4-sulfonatophenyl)porphine, the (Bu3Sn)4TPPS and the (Bu2Sn)2TPPS. In particular, in treated melanoma cell lines we showed an increase of cell cycle arrest at G0/G1 or G2/M phase and the inhibition of cell colony formation. Notably, the (Bu3Sn)4TPPS and (Bu2Sn)2TPPS treatment of melanoma cells decreases the expression and activation of FAK, the expression of BRAF, HLA-DR and STAT3 as well as the cell migration through Boyden chambers with differential media compartmentalization. The results obtained, suggested that (Bu3Sn)4TPPS and (Bu2Sn)2TPPS could be used as adjuvant therapeutic agents for their role in the regression of melanoma motility and metastatic dissemination