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.
Vyas
Sharda
S
Department of Anatomy, Loma Linda University, School of Medicine, CA 92350, USA.
Asmerom
Yayesh
Y
De León
Daisy D
DD
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms; D002402:Cathepsin D / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000502:physiology*; D009376:Neoplasms, Hormone-Dependent; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013267:Stilbenes; D007335:Insulin-Like Growth Factor II; D002402:Cathepsin D; D000077185:Resveratrol