Chemoprevention by lipid-soluble tea polyphenols in diethylnitrosamine/phenobarbital-induced hepatic pre-cancerous lesions

Anticancer Res. 2014 Feb;34(2):683-93.

Abstract

Background: Green tea polyphenols (GTPs) have been proposed as promising candidates for chemoprevention. However, GTPs levels are maintained relatively low in the blood and are chemically-unstable. Lipid-soluble tea polyphenols (LTPs) are products of modified GTPs with ester linkage with fatty acids. LTPs are lipophilic and expected to provide improved absorption and utilization in the body compared with water-soluble polyphenols. The current study was designed to investigate the chemo-preventive property and the possible mechanisms of LTP action against diethylnitrosamine (DEN)-induced liver cancer in rats.

Materials and methods: Oral administration of LTPs at doses of 0, 40, and 400 mg/kg/day was initiated 2 weeks prior to DEN injection and was continued for 30 weeks. At that time point samples were collected and liver histopathological analyses were performed.

Results: LTPs decreased the area and number of placental glutathione S-transferase-positive foci in liver samples of DEN-treated rats. Furthermore, LTPs counteracted DEN-induced fibrosis formation in liver. Immunohistochemical staining of rat liver showed that LTPs inhibited DEN-mediated elevations in numbers of cells positive for PCNA and 8-OHdG.

Conclusion: For the first time, the present study demonstrated, that LTPs exert a chemo-preventive effect against precancerous lesions through inhibition of cellular proliferation and DNA damage in a rat liver model.

Keywords: DNA damage; GTPs; LTPs; precancerous lesions; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Growth Processes / drug effects
  • DNA Damage
  • Diethylnitrosamine
  • Immunohistochemistry
  • Lipids / chemistry
  • Liver / drug effects
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / pathology
  • Liver Neoplasms, Experimental / chemically induced
  • Liver Neoplasms, Experimental / pathology
  • Liver Neoplasms, Experimental / prevention & control*
  • Male
  • Organ Size / drug effects
  • Phenobarbital
  • Polyphenols / chemistry
  • Polyphenols / pharmacology*
  • Precancerous Conditions / chemically induced
  • Precancerous Conditions / drug therapy*
  • Precancerous Conditions / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Solubility
  • Tea / chemistry*

Substances

  • Lipids
  • Polyphenols
  • Tea
  • Diethylnitrosamine
  • Phenobarbital