Insulin-like growth factor II mediates resveratrol stimulatory effect on cathepsin D in breast cancer cells.

Cathepsin D (CD) is an enzyme that promotes breast cancer. CD is stored intracellularly; however, we demonstrated that IGF-II promotes CD secretion in estrogen receptor positive (ER+) breast cancer cells. We also showed that resveratrol (RSV) stimulates IGF-II in ER(+) breast cancer cells. Thus, we designed this study to determine whether RSV regulates CD in MCF-7, T47D (ER+) breast cancer cells as well as in Hs578t (cancer) and MCF-10A (normal) ER - cell lines. RSV (10(- 6) M) increased CD and IGF-II secretion in ER+ but not ER - cells. RSV treatment (10(- 4) M) inhibited CD in ER+ but not in ER - cells. Transfection of ER - cells with proIGF-II increased CD secretion. RSV (10(- 6) M) modulates CD secretion through IGF-II while RSV (10(- 4) M) inhibits CD in ER+ but not ER - cells. Regulation of CD by RSV represents a novel mechanism by which RSV may protect against breast cancer.