Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator.
Resveratrol is a naturally occurring product found in grapes and wine. The effect of synthetic resveratrol on the growth of estrogen receptor (ER)-positive (KPL-1 and MCF-7) and -negative (MKL-F) human breast cancer cell lines was examined. Resveratrol at low concentrations caused cell proliferation in ER-positive lines (KPL-1, < or = 22 microM; MCF-7, < or = 4 microM) whereas at high concentrations (> or = 44 microM) it caused suppression of cell growth in all three cell lines examined. Growth suppression was due to apoptosis as seen by the appearance of a sub-G1 fraction. The apoptosis cascade up-regulated Bax and Bak protein, down-regulated Bcl-xL protein, and activated caspase-3. Resveratrol (52-74 microM) antagonized the effect of linoleic acid, a potent breast cancer cell stimulator, and suppressed the growth of both ER-positive and -negative cell lines. Thus, resveratrol could be a promising anticancer agent for both hormone-dependent and hormone-independent breast cancers, and may mitigate the growth stimulatory effect of linoleic acid in the Western-style diet.
Nakagawa
H
H
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
Kiyozuka
Y
Y
Uemura
Y
Y
Senzaki
H
H
Shikata
N
N
Hioki
K
K
Tsubura
A
A
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D019787:Linoleic Acid / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D016588:Anticarcinogenic Agents; C494772:BAK1 protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D013267:Stilbenes; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019787:Linoleic Acid; D000077185:Resveratrol