Neoxanthin, a major
carotenoid in green leafy vegetables, was reported to exhibit potent antiproliferative effect via apoptosis induction on human
prostate cancer cells. However, the metabolic fate of dietary
neoxanthin in mammals remains unknown. In the present study, we investigated the gastrointestinal metabolism of
neoxanthin in mice and the in vitro digestion of spinach, and estimated the antiproliferative effect of
neoxanthin metabolites on PC-3 human
prostate cancer cells. Two hours after the
oral administration to mice of purified
neoxanthin, unchanged
neoxanthin and stereoisomers of
neochrome (8'-R/S) were detected in the plasma, liver, and small intestinal contents. To estimate the effect of intragastric acidity on the conversion of dietary
neoxanthin into
neochrome (
epoxide-furanoid rearrangement), spinach was digested in vitro by incubating it with a
pepsin-HCl
solution at pH 2.0 or 3.0 (gastric phase) followed by a
pancreatin-
bile salt solution (intestinal phase). Spinach
neoxanthin was largely converted into (R/S)-
neochrome during the digestion when the gastric phase was set at pH 2.0, whereas the rearrangement was observed to a lesser extent at pH 3.0. (R/S)-
neochrome dose-dependently inhibited the proliferation of PC-3 cells as well as
neoxanthin at concentrations < or = 20 micromol/L. Although
neoxanthin induced evident apoptotic cell death, (R/S)-
neochrome inhibited the cell proliferation without obvious apoptosis induction. These results indicate that dietary
neoxanthin is partially converted into (R/S)-
neochrome by intragastric acidity before intestinal absorption and that (R/S)-
neochrome exhibits an antiproliferative effect on PC-3 cells by the induction of cytostasis.