[CAS NO. 123653-11-2]  NS-398 (NS398)

NS-398 inhibits COX-2 enzyme activity in a concentration dependent manner, the IC50 being 3.8 μM, whereas NS-398 at 100μM has no effect on COX-1 activity. At 10 μM, NS-398 treatment results in increased production of COX-2 and the pro-inflammatory cytokine. NS-398 (10 μM) induces apoptosis in LNCaP cells, but not in the more aggressive, androgen-unresponsive C4-2b cells. The C4-2b cells are observed to continue to proliferate when treated with NS-398 and continues to retain malignant phenotype characteristics. NS-398 treatment results in C4-2b cell differentiation into an unusual neuroendocrinelike cell. These neuroendocrine-like cells produces both epithelial (cytokeratin 18 and prostate specific antigen) and neuronal (neuron-specific enolase and chromogranin A) proteins. Furthermore, this C4-2b cellular response to NS-398 is mediated by NF-kB transcription factor activation. NS-398 induces NF-kB and down-regulates Ikβ-α protein expression in LNCaP C4-2b cells.