JNK inhibitor blocks caspase-3 cleavage and abrogates PS-341–induced apoptosis in MM.1S cells.

(A) Inhibition of PS-341–induced JNK phosphorylation, but not of MDM2 expression or p53 phosphorylation, by JNK inhibitor SP600125. (B) Caspase-3 cleavage triggered by PS-341 is dependent on JNK activity. SP600125 inhibits the phosphorylation of JNK and caspase-3 cleavage triggered by PS-341. (C) Cell death triggered by PS-341 is partially dependent on JNK activation. MM.1S cell death triggered by PS-341 was measured by MTT assay, in the absence (■) or presence of 5 μM (░) and 10 μM (▪) SP600125. *P < .01 (versus 0 μM).