Chemopreventive effect of selenium and Chinese medicinal herbs on N-nitrosobis(2-oxopropyl)amine-induced hepatocellular carcinoma in Syrian hamsters

Liver Int. 2008 Jul;28(6):841-55. doi: 10.1111/j.1478-3231.2008.01698.x.

Abstract

Background/aims: Oxidative DNA damage by reactive oxygen species is involved in the process of liver carcinogenesis. To test the hypothesis that a remedy containing Scutellaria baicalensis Georgi (Sb) and Bupleurum scorzonerifolfium Willd (Bs) (Sb/Bs remedy) modulates hepatic neoplastic growth, BOP (N-nitrosobis(2-oxopropyl)amine)-induced liver cancers in hamsters were established.

Methods: Parameters such as survival rate, tumour area, tumour foci, 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, transforming growth factor (TGF-beta1) and tumour necrosis factor-alpha (TNF-alpha) were measured after Sb/Bs remedy treatment during BOP-induced carcinogenesis.

Results: The results showed that the Sb/Bs remedy and its constituents Sb and Bs suppressed the tumour area in BOP-induced liver tumours. Because selenium (Sel) is toxic at a high dose (10 mg/kg), with a low survival rate (0%), the combination of Sb/Bs remedy and low-dose Sel (1 mg/kg) was found to decrease the tumour area and the number of tumour foci while increasing serum TNF-alpha and TGF-beta1, but not IL-6 levels. Besides, the Sb/Bs remedy, when combined with low-dose Sel, not only decreased the expression of 8-OHdG and increased caspase-3 expression within the glutathione S-transferase placental form-positive tumour foci but also increased tumour apoptosis in BOP-induced hamsters.

Conclusions: We conclude that low-dose Sel has a chemoprevention effect on BOP-induced liver tumours and such an effect was more enhanced when combined with Sb/Bs treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Anticarcinogenic Agents / therapeutic use*
  • Biomarkers, Tumor / blood
  • Carcinoma, Hepatocellular / chemically induced
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / prevention & control*
  • Caspase 3 / blood
  • Chemoprevention
  • Cricetinae
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / blood
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Drugs, Chinese Herbal / therapeutic use*
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / pathology
  • Liver Neoplasms / prevention & control*
  • Longevity / drug effects
  • Male
  • Mesocricetus
  • Nitrosamines
  • Selenium / therapeutic use*
  • Transforming Growth Factor beta1 / blood
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Anticarcinogenic Agents
  • Biomarkers, Tumor
  • Drugs, Chinese Herbal
  • Nitrosamines
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • nitrosobis(2-oxopropyl)amine
  • 8-Hydroxy-2'-Deoxyguanosine
  • Caspase 3
  • Deoxyguanosine
  • Selenium