Resveratrol is a naturally occurring anticancer compound present in grapes and wine with antiproliferative properties against
breast cancer cells and xenografts. Our objective was to investigate the metabolic alterations that characterize the effects of
resveratrol in the human
breast cancer cell lines MCF-7 and MDA-MB-231 using high-throughput liquid chromatography-based mass spectrometry. In both cell lines, growth inhibition was dose dependent and accompanied by substantial metabolic changes. For all 21
amino acids analyzed levels increased more than 100-fold at a
resveratrol dose of 100 μM with far lower concentrations in MDA-MB-231 compared to MCF-7 cells. Among the
biogenic amines and modified
amino acids (n = 16)
resveratrol increased the synthesis of
serotonin,
kynurenine, and spermindine in both cell lines up to 61-fold indicating that
resveratrol strongly interacts with cellular
biogenic amine metabolism. Among the
eicosanoids and oxidized
polyunsaturated fatty acids (n = 17) a pronounced increase in
arachidonic acid and its metabolite 12S-HETE was observed in MDA-MB-231 and to a lesser extent in MCF-7 cells, indicating release from cell membrane
phospholipids upon activation of
phospholipase A₂ and subsequent metabolism by
12-lipoxygenase. In conclusion, metabolomic analysis elucidated several small molecules as markers for the response of
breast cancer cells to
resveratrol.