RT Journal Article
SR Electronic
T1 BIOTRANSFORMATION OF FUCOXANTHINOL INTO AMAROUCIAXANTHIN A IN MICE AND HEPG2 CELLS: FORMATION AND CYTOTOXICITY OF FUCOXANTHIN METABOLITES
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 205
OP 211
DO 10.1124/dmd.32.2.205
VO 32
IS 2
A1 Akira Asai
A1 Tatsuya Sugawara
A1 Hiroshi Ono
A1 Akihiko Nagao
YR 2004
UL http://dmd.aspetjournals.org/content/32/2/205.abstract
AB 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 (10,000gsupernatant 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-β,ϵ-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-βend group of fucoxanthinol into the 6′-hydroxy-3′-oxo-ϵend 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 μM 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. The American Society for Pharmacology and Experimental Therapeutics