Cancer Chemotherapy and Pharmacology

, Volume 60, Issue 2, pp 257–266

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

  • Hong Cai
  • David J. Boocock
  • William P. Steward
  • Andreas J. Gescher
Original Article

DOI: 10.1007/s00280-006-0368-5

Cite this article as:
Cai, H., Boocock, D.J., Steward, W.P. et al. Cancer Chemother Pharmacol (2007) 60: 257. doi:10.1007/s00280-006-0368-5

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.

Keywords

Flavonoids Chemoprevention Metabolism 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Hong Cai
    • 1
  • David J. Boocock
    • 1
  • William P. Steward
    • 1
  • Andreas J. Gescher
    • 1
  1. 1.Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular MedicineUniversity of LeicesterLeicesterUK