Figure 5.

Effects of inhibition of IGF-IR on downstream targets in MCL cell lines. At 24 h, PPP induced a concentration-dependent down-regulation of pAkt and pIRS-1 without affecting their basal levels in the Mino cell line (A). PPP also decreased pCdc2 and increased cyclin B1, which is consistent with the occurrence of G2/M-phase cell cycle arrest. In support of apoptotic cell death, PPP caused cleavage of caspase-3, caspase-8, caspase-9, and PARP, which was associated with a decrease in their basal levels. Treatment with PPP was also associated with cytochrome c release resulting in increased cytosolic [C] fraction and decreased mitochondrial [M] fraction (A). Treating MCL cell lines with IGF-IR siRNA, and not control scrambled siRNA, for 48 h induced similar effects on some of these proteins and, in addition, decreased pJnk and cyclin D1 levels (B).