Fucoxanthin, a major
carotenoid in edible brown algae, potentially inhibits the proliferation of human
prostate cancer cells via apoptosis induction. However, it has been postulated that dietary
fucoxanthin is hydrolyzed into
fucoxanthinol in the gastrointestinal tract before absorption in the intestine. In the present study, we investigated the further biotransformation of orally administered
fucoxanthin and estimated the cytotoxicity of
fucoxanthin metabolites on PC-3 human
prostate cancer cells. After the
oral administration of
fucoxanthin in mice, two metabolites,
fucoxanthinol and an unknown metabolite, were found in the plasma and liver. The unknown metabolite was isolated from the incubation mixture of
fucoxanthinol and mouse liver preparation (10,000 g supernatant of homogenates), and a series of instrumental analyses identified it as
amarouciaxanthin A [(3S,5R,6'S)-3,5,6'-trihydroxy-6,7-didehydro-5,6,7',8'-tetrahydro-beta,epsilon-
carotene-3',8'-dione]. The conversion of
fucoxanthinol into
amarouciaxanthin A was predominantly shown in liver microsomes. This dehydrogenation/isomerization of the 5,6-epoxy-3-hydroxy-5,6-dihydro-beta end group of
fucoxanthinol into the 6'-hydroxy-3'-oxo-epsilon end group of
amarouciaxanthin A required
NAD(P)+ as a cofactor, and the optimal pH for the conversion was 9.5 to 10.0.
Fucoxanthinol supplemented to culture medium via HepG2 cells was also converted into
amarouciaxanthin A. The 50% inhibitory concentrations on the proliferation of PC-3 human
prostate cancer cells were 3.0, 2.0, and 4.6 microM for
fucoxanthin,
fucoxanthinol, and
amarouciaxanthin A, respectively. To our knowledge, this is the first report on the enzymatic dehydrogenation of a 3-hydroxyl end group of
xanthophylls in mammals.