Resveratrol regulates insulin-like growth factor-II in breast cancer cells.
IGF-II is a potent mitogen and inhibitor of apoptosis in breast cancer. Regulation of IGF-II is complex and includes inhibition by tumor suppressors, stimulation by oncogenes, and imprinting and hormonal regulation by estrogens. Resveratrol (RSV) is a phytoestrogen that displays estrogen-like agonistic and antagonistic activity. Recent studies have shown that RSV inhibits the growth of breast cancer cells and may represent a potent agent in chemopreventive therapy. Because 17beta-estradiol regulates IGF-II, we hypothesized that RSV may have a similar effect on IGF-II. The present study was designed to examine whether: 1) RSV modulates IGF-II in breast cancer cells; 2) regulation of IGF-II by RSV is dependent on the ER status; and 3) IGF-II (not IGF-I) mediates RSV effects on breast cancer cells. Treatment of MCF-7 and T47D cells with RSV (10(-6) M) caused stimulation of precursor IGF-II mRNA and protein; this effect was blocked by coincubation with 17beta-estradiol (10(-9) M). Cell growth stimulated by RSV (10(-6) M) was blocked by addition of a blocking IGF-I receptor antibody, or the antiestrogen tamoxifen (10(-7) M). In contrast, RSV treatment (10(-4) M) inhibited IGF-II secretion and cell growth in MCF-7 and T47D cells. No increase in IGF-II levels is seen in estrogen receptor (-) MCF-10 cells, even though cell growth was inhibited by RSV 10(-4) M and precursor IGF-II blocked the inhibitory effect of resveratrol. No change in IGF-I was observed with RSV treatment (10(-6) to 10(-4) M). Our study demonstrates that RSV regulates IGF-II and that IGF-II mediates RSV effect on cell survival and growth in breast cancer cells.
Vyas
Sharda
S
Department of Anatomy, CSP 11012, Loma Linda University, Loma Linda, California 92350, USA.
Asmerom
Yayesh
Y
De León
Daisy D
DD
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D012333:RNA, Messenger; D013267:Stilbenes; D007335:Insulin-Like Growth Factor II; D000077185:Resveratrol