Figure 5.

Mevalonate reversal of lovastatin, lovastatin pro-drug, and lactacystin. (A) MDA-MB-157 cells were treated with the indicated concentration of lovastatin (lov) or the pro-drug in the presence or absence of 4 mM mevalonate (Mev) for 36 hr and subjected to flow cytometric measurements of DNA content. (B) MDA-MB-157 cells were treated with 10 μM lactacystin (lact) in the presence or absence of 10 mM or 50 mM mevalonate for 36 hr. At the end of treatment cells were subjected to flow cytometric measurement of DNA content. Percent apoptosis reflects the accumulation of cells with sub-G₁ DNA content. (Apoptosis also was measured by chromosome condensation/4′,6-diamidino-2-phenylindole staining; data not shown.) (C) Induction of the proteasome activity by mevalonate. MDA-MB-436 (closed symbols) and MDA-MB-157 (open symbols) were treated with the indicated concentrations of mevalonate for 36 hr. After treatment, crude cell extracts were prepared and assayed for proteasome enzyme activity by measuring the chymotrypsin-like activity of the proteasome (described for Fig. 4B). Values are expressed as fold increase over no treatment controls. n = 3, and the averages of the values are indicated.