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A novel antihepatitis drug, bicyclol, prevents liver carcinogenesis in diethylnitrosamine-initiated and phenobarbital-promoted mice tumor model.

Sun H, Yu L, Wei H, Liu G - J. Biomed. Biotechnol. (2012)

Bottom Line: Pretreatment with bicyclol showed a marked reduction in the above condition.Bicyclol also decreased the expression of AFP and proliferating cell nuclear antigen level in the liver tissue and attenuated the decrease in body weight.These results further indicate that bicyclol has the chemopreventive potential for liver carcinogenesis induced by carcinogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China. sunhua@imm.ac.cn

ABSTRACT
Bicyclol, an antihepatitis drug developed by Chinese scientists, has been shown to prevent the malignant transformation induced by 3-methylcholanthrene and 12-O-tetradecanoylphorbol-13-acetate in WB-F344 rat liver epithelial cells. This study provides further evidence on its role as a chemopreventive agent in experimental mice with diethylnitrosamine- (DEN-) initiated and phenobarbital- (PB-) promoted liver carcinoma. Liver tissue and serum were collected. In the two-stage model of hepatocarcinogenesis in mice, oral administration of bicyclol (100, 200 mg/kg) before DEN injection showed significant reduction in the incidence of hepatocellular foci, nodules, or carcinoma. Histopathological examination revealed that there was no hepatocellular carcinoma (HCC) and hepatoma formation in the mice pretreated with bicyclol (200 mg/kg) at week 20, while the mice treated with DEN/PB developed 33.3% HCC and 55.6% hepatoma. Furthermore, the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and α-fetal protein (AFP) in serum significantly increased in the DEN/PB model group in comparison with the control group. Pretreatment with bicyclol showed a marked reduction in the above condition. Bicyclol also decreased the expression of AFP and proliferating cell nuclear antigen level in the liver tissue and attenuated the decrease in body weight. In this study, we also found that 10 weeks after stopping the administration of PB and drugs, the control and bicyclol-treated (200 mg/kg) animals showed no HCC and hepatoma formation at the time of termination whereas DEN/PB-induced mice developed 100% hepatoma and 50% HCC. These results further indicate that bicyclol has the chemopreventive potential for liver carcinogenesis induced by carcinogens.

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Body weight profile in the control and experimental groups. Average values with standard deviations are shown. n = 14-15.
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fig3: Body weight profile in the control and experimental groups. Average values with standard deviations are shown. n = 14-15.

Mentions: The chemopreventive effect of bicyclol on DEN/PB-induced hepatocellular cancer was elucidated in male ICR mice. At week 20, DEN/PB-induced tumors or nodules could be readily observed by unaided eyes (Figure 2(a)). All macroscopically visible liver nodules greater than approximately 1 mm in diameter were counted. Oral administration of bicyclol before tumor initiation resulted in a marked inhibition of tumor development in the animals. The average number of nodules per liver in the bicyclol-treated groups was significantly lower than those in the DEN/PB model group (Figure 2(b)). In addition, the body weight of the animals decreased on DEN/PB administration when compared to the control group. Pretreatment with bicyclol prevented the decrease in body weight (Figure 3).


A novel antihepatitis drug, bicyclol, prevents liver carcinogenesis in diethylnitrosamine-initiated and phenobarbital-promoted mice tumor model.

Sun H, Yu L, Wei H, Liu G - J. Biomed. Biotechnol. (2012)

Body weight profile in the control and experimental groups. Average values with standard deviations are shown. n = 14-15.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3303747&req=5

fig3: Body weight profile in the control and experimental groups. Average values with standard deviations are shown. n = 14-15.
Mentions: The chemopreventive effect of bicyclol on DEN/PB-induced hepatocellular cancer was elucidated in male ICR mice. At week 20, DEN/PB-induced tumors or nodules could be readily observed by unaided eyes (Figure 2(a)). All macroscopically visible liver nodules greater than approximately 1 mm in diameter were counted. Oral administration of bicyclol before tumor initiation resulted in a marked inhibition of tumor development in the animals. The average number of nodules per liver in the bicyclol-treated groups was significantly lower than those in the DEN/PB model group (Figure 2(b)). In addition, the body weight of the animals decreased on DEN/PB administration when compared to the control group. Pretreatment with bicyclol prevented the decrease in body weight (Figure 3).

Bottom Line: Pretreatment with bicyclol showed a marked reduction in the above condition.Bicyclol also decreased the expression of AFP and proliferating cell nuclear antigen level in the liver tissue and attenuated the decrease in body weight.These results further indicate that bicyclol has the chemopreventive potential for liver carcinogenesis induced by carcinogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China. sunhua@imm.ac.cn

ABSTRACT
Bicyclol, an antihepatitis drug developed by Chinese scientists, has been shown to prevent the malignant transformation induced by 3-methylcholanthrene and 12-O-tetradecanoylphorbol-13-acetate in WB-F344 rat liver epithelial cells. This study provides further evidence on its role as a chemopreventive agent in experimental mice with diethylnitrosamine- (DEN-) initiated and phenobarbital- (PB-) promoted liver carcinoma. Liver tissue and serum were collected. In the two-stage model of hepatocarcinogenesis in mice, oral administration of bicyclol (100, 200 mg/kg) before DEN injection showed significant reduction in the incidence of hepatocellular foci, nodules, or carcinoma. Histopathological examination revealed that there was no hepatocellular carcinoma (HCC) and hepatoma formation in the mice pretreated with bicyclol (200 mg/kg) at week 20, while the mice treated with DEN/PB developed 33.3% HCC and 55.6% hepatoma. Furthermore, the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and α-fetal protein (AFP) in serum significantly increased in the DEN/PB model group in comparison with the control group. Pretreatment with bicyclol showed a marked reduction in the above condition. Bicyclol also decreased the expression of AFP and proliferating cell nuclear antigen level in the liver tissue and attenuated the decrease in body weight. In this study, we also found that 10 weeks after stopping the administration of PB and drugs, the control and bicyclol-treated (200 mg/kg) animals showed no HCC and hepatoma formation at the time of termination whereas DEN/PB-induced mice developed 100% hepatoma and 50% HCC. These results further indicate that bicyclol has the chemopreventive potential for liver carcinogenesis induced by carcinogens.

Show MeSH
Related in: MedlinePlus