Chemopreventive effect of selenium and Chinese medicinal herbs on N-nitrosobis(2-oxopropyl)amine-induced hepatocellular carcinoma in Syrian hamsters.
OBJECTIVE
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.
Lee
Chang-Yin
CY
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Hsu
Yi-Chao
YC
Wang
Jir-You
JY
Chen
Chien-Chih
CC
Chiu
Jen-Hwey
JH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D053148:Caspase 3 / Q000097:blood; D018890:Chemoprevention; D006224:Cricetinae; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008136:Longevity / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines; D012643:Selenium / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D004365:Drugs, Chinese Herbal; D009602:Nitrosamines; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C013622:nitrosobis(2-oxopropyl)amine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D053148:Caspase 3; D003849:Deoxyguanosine; D012643:Selenium