FIGURE 4.

Selective inhibition of the proteasomal CT-L activity in whole cells, accumulation of proteasome substrate proteins, inhibition of cell survival pathways, and induction of apoptosis. A, exponentially growing human breast cancer MDA-MB-468 cells were treated with 5 μm PI-1840 for the indicated time points, followed by measurement of CT-L, T-L, and PGPH activities in whole cell extracts as described under “Experimental Procedures.” B and C, human breast cancer MDA-MB-468 cells were treated with the indicated concentrations of PI-1833 and PI-1840 for 48 h, followed by Western blot assay using the indicated antibodies as described under “Experimental Procedures.” Data are representative of at least two independent experiments. PARP, poly(ADP-ribose) polymerase. Lane D, DMSO.