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Biotransformation of 5‐demethyltangeretin in mice: generation of anti‐cancer metabolites
Author(s) -
Wu Xian,
Sun Yue,
Wang Minqi,
Gao Zili,
Song Mingyue,
Xiao Hang
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.145.1
Subject(s) - biotransformation , metabolite , demethylation , chemistry , hydroxylation , glucuronide , metabolism , apoptosis , biochemistry , primary metabolite , metabolic pathway , cancer cell , cancer , biology , enzyme , gene , gene expression , genetics , dna methylation
5‐demethyltangeretin (5DT) is a unique polymethoxyflavone isolated from citrus peels, and showed potent inhibitory effects on various human cancer cells. Biotransformation of dietary bioactive components plays critical roles in their biological activities because they can be transformed to metabolites with significant bioactivities. In this study, we determined the metabolic fate of 5DT in mice and determined the bioactivities of its major metabolite. Our results showed that 5DT underwent extensive biotransformation in mice fed with 5DT, and produced demethylated and hydroxylated metabolites via phase I metabolism, and glucuronide and sulfate conjugates via phase II metabolism. In particular, 4′ position on the B‐ring of 5DT was the primary site for demethylation (formation of xanthomicrol, XAN), and 3′ position on the B‐ring was the primary site for hydroxylation (formation of 5, 3′, 4′‐tridemethyltangeretin, TDT). Interestingly, the colonic levels of XAN was much higher than that of 5DT. Therefore, we further investigated the inhibitory effects of XAN on human colon cancer cells. It was found that XAN significantly inhibited the colon cancer cell growth by inducing G2 phase cell cycle arrest and cellular apoptosis. Overall, this study identified major metabolites of 5DT, and demonstrated the anti‐cancer potential of the metabolites. Support or Funding Information This study was supported by funding from USDA.Biotransformation pathways of 5‐demethyltangeretin (5DT)