Tissue distribution in mice and metabolism in murine and human liver of apigenin and tricin, flavones with putative cancer chemopreventive properties

Cancer Chemother Pharmacol. 2007 Jul;60(2):257-66. doi: 10.1007/s00280-006-0368-5. Epub 2006 Nov 7.

Abstract

Purpose: The flavones apigenin and tricin, which occur in leafy vegetables and rice bran, respectively, possess cancer chemopreventive properties in preclinical rodent models. Their pharmacology is only poorly understood. We compared their tissue levels in mice in vivo and their metabolism in liver fractions in vitro.

Methods: Mice received apigenin or tricin (0.2%) with their diet for 5-7 days, and flavone levels were compared in the plasma, liver and gastrointestinal mucosa using HPLC-UV. Flavone metabolism was investigated in murine and human liver microsomes or cytosol in vitro co-incubated with uridine 5'-diphosphoglucuronic acid or 3'-phosphoadenosine-5' phosphosulfate. Flavone metabolites were characterized by on-line HPLC-mass spectrometry.

Results: After dietary administration of flavones for 7 days, levels of tricin in plasma, liver and mucosa exceeded those of apigenin by 350, 33 and 100%, respectively. Apigenin was more rapidly glucuronidated than tricin in liver microsomes, whilst tricin underwent swifter sulfonation than apigenin in liver cytosol. For either flavone the rate of glucuronidation was much faster than that of sulfonation. Flavone monoglucuronides and monosulfates were identified as metabolites in microsomal and cytosolic incubations, respectively.

Conclusions: When consumed with the diet in mice tricin seems to be more available than apigenin in blood and tissues. Differences in their glucuronidation may account for their differential availability. Thus tricin may have a pharmacokinetic advantage over apigenin. This type of information may help decide which flavonoids to select for clinical development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / analysis
  • Antineoplastic Agents / pharmacokinetics*
  • Apigenin / analysis
  • Apigenin / pharmacokinetics*
  • Chemoprevention
  • Chromatography, High Pressure Liquid
  • Cytosol / metabolism
  • Flavonoids / analysis
  • Flavonoids / pharmacokinetics*
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Spectrometry, Mass, Electrospray Ionization
  • Tissue Distribution

Substances

  • Antineoplastic Agents
  • Flavonoids
  • Apigenin
  • tricin