Decursin inhibits EGFR‐ERK1/2 signaling axis in advanced human prostate carcinoma cells

The study has shown that decursin, a coumarin compound, induces cell cycle arrest and apoptosis in human prostate cancer cells (PCa); however, its molecular mechanisms are largely unexplored. Therefore, the author studied the mechanisms associated with its anticancer activity in advanced human prostate carcinoma cells. The study found that decursin inhibited epidermal growth factor receptor (EGFR) signaling by inhibiting its activating phosphorylation at tyrosine 1068 residue in DU145 and 22Rv1 cells. Furthermore, this inhibition of EGFR was associated with the downregulation of ERK1/2 phosphorylation. Decursin decreased EGF ligand-induced phosphorylation of EGFR (Y-1068) and activation of its downstream mediator, ERK1/2. Furthermore, inhibitory targeting of the EGFR-ERK1/2 axis by combinatorial treatment of decursin and erlotinib further sensitized DU145 cells for decursin-induced growth inhibition and cell death. Overall, these findings strongly suggest that the anticancer efficacy of decursin against human PCa involves inhibitory targeting of the EGFR-ERK1/2 signaling axis, a pathway constitutively active in advanced PCa.