Biotransformation of fucoxanthinol into amarouciaxanthin a in mice and HepG2 cells: Formation and cytotoxicity of fucoxanthin metabolites

Akira Asai, Tatsuya Sugawara, Hiroshi Ono, Akihiko Nagao

Research output: Contribution to journalArticlepeer-review

143 Citations (Scopus)

Abstract

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 (10,000g 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-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-β end group of fucoxanthinol into the 6′-hydroxy-3′-oxo-ε 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 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.

Original languageEnglish
Pages (from-to)205-211
Number of pages7
JournalDrug Metabolism and Disposition
Volume32
Issue number2
DOIs
Publication statusPublished - 2004 Feb

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Biotransformation of fucoxanthinol into amarouciaxanthin a in mice and HepG2 cells: Formation and cytotoxicity of fucoxanthin metabolites'. Together they form a unique fingerprint.

Cite this