Biotransformation of Fucoxanthinol Into Amarouciaxanthin a in Mice and Hepg2 Cells: Formation and Cytotoxicity of Fucoxanthin Metabolites

Abstract

This article is available online at http://dmd.aspetjournals.org 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,6S)-3,5,6-trihydroxy-6,7-didehydro-5,6,7,8-tetrahydro-␤,⑀-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-␤ end group of fucoxanthinol into the 6-hydroxy-3-oxo-⑀ 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 M 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.

Fucoxanthin and its metabolite, fucoxanthinol, suppress adipocyte differentiation in 3T3-L1 cells

“…In addition, the carotenoid accumulation in 3T3-L1 cells was greater following treatment with fucoxanthinol than after treatment with fucoxanthin. Sugawara et al (24) and Asai et al (25) also reported that orally administered fucoxanthin is detected as fucoxanthinol and amarouciaxanthin A in the blood and liver. Therefore, we examined the suppressive effects of fucoxanthinol on 3T3-L1 adipocyte differentiation.…”

Metabolomics of carotenoids: The challenges and prospects – A review

“…The characterization of centric/eccentric cleavages, the formation of apocarotenoids, and oxidative products of pro-vitamin and nonprovitamin A carotenoids is given a platform for metabolomics. As evident from available research reports, carotenoids are biologically converted into metabolites by enzymatic cleavages, oxidation, reduction, hydrolysis and by active reaction with free radicals (Olson, 1994;Nagao, 2004;Lakshminarayana et al, 2008) (Fig. 1).…”

“…In addition, peroxidases and lipoxygenases are also reported to form apocarotenoids (Yeum et al, 1995). Other than the enzymatic cleavages, non-enzymatic processes can also cause oxidative cleavages of carotenoids to form various oxidative products (Nagao, 2004).…”

“…Sugawara, Baskaran, Tuzuki, and Nagao (2002) have shown the formation of fucoxanthinol in the intestinal tract and demonstrated the dietary fucoxanthin was deacetylated by lipase and esterase from the pancreas or in intestinal cells. Asai, Sugawara, Ono, and Nagao (2004) reported biotransformation of fucoxanthinol in ICR mice and HepG2 cells. In addition, they also showed the bioconversion of fucoxanthinol into amarouciaxanthin-A through dehydrogenation/isomerization.…”

“…APCI has become the most widely used ionization technique for various carotenoids because of high sensitivity (Rivera et al, 2011). Several metabolites of carotenoids were identified and characterized by using LC-MS in APCI ionization mode (Lakshminarayana et al, 2008;Bhosale et al, 2007;Yonekura et al, 2010;Asai et al, 2004;Sangeetha et al, 2009a,b;Sicilia et al, 2005) ( Table 1). The main drawback of LC-MS is closely eluting isobars, and isomers are indistinguishable by using this method.…”