Antiproliferative Effect of Rottlerin on Sk-Mel-28 Melanoma Cells

摘要: Melanoma is the most aggressive and chemoresistant form of skin cancer. Mutated, constitutively active B-RAF believed to play a crucial role, although selective inhibition has shown poor clinical success, since phenomena resistance usually occur, likely arising from additional genetic aberrations, such as loss function p53 PTEN, overexpression cyclin D1, hyperactivation NF-κB, downregulation p21/Cip1. Since all them are present in Sk-Mel-28 melanoma cells, this cell line could be an ideal, albeit hard study, model develop new therapeutic strategies. In current we tested cytostatic action Rottlerin on basis known effects main proliferative signaling pathways. We presented evidence that drug inhibits growth by Akt- p21/Cip1-independent mechanism, involving dual ERK NF-κB D1. addition, found increases phosphorylation, but, surprisingly, resulted decreased activity. Pull-down experiments, using Rottlerin-CNBr-conjugated Sepharose beads, revealed binds ERK, independently its phosphorylation status. This direct interaction part explain paradoxical blockage downstream arrest. would like dedicate paper memory our friend colleague, prematurely deceased, Claudia Torricelli, who actively contributed project.