Despite public awareness and availability of sunscreen, incidence and mortality rates for malignant melanoma continue to increase every year. Novel strategies are required to prevent melanoma development as the causes for ∼60% of cases remaining unknown. While sunscreen is effective at protecting skin from UV radiation induced damage, inhibiting melanocytic lesion development using body creams or sunscreens containing chemopreventive agents could be a novel approach to fight this disease. Hence, the chemopreventive efficacy of PBISe, a selenium containing isosteric analogue of PBIT, has been examined in laboratory generated skin reconstructs and melanoma tumor xenograft models. The data demonstrate that PBISe treated skin reconstructs containing melanocytic lesion cells had 60–70% smaller tumor lesions compared to control treated skins. Furthermore, mice topically treated with PBISe had ∼50% fewer tumors compared to PBIT or acetone vehicle treated control groups. Mechanistically, PBISe elevated MAP kinase pathway activity as indicated by increased pErk1/2 levels to amounts that induced cellular senescence. Furthermore, PBISe treatment down‐regulated cyclin‐D1, upregulated the expression of cell cycle inhibitors p21 and p27 as well as apoptotic markers cleaved caspase‐3 and PARP to inhibit cell proliferation and induce apoptosis. In conclusion, the results demonstrate the potential utility of topical PBISe application for preventing melanoma leision development.

Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A96.

Copyright © 2009, American Association for Cancer Research
2009