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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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Expression of PCNA in the control and experimental groups at week 20. (a) Representative microscopic pictures of PCNA-stained liver sections by immunohistochemical analysis (100×) and quantification of the immunostained section of PCNA. ##P < 0.01 compared with the control group; *P < 0.05, **P < 0.01 compared with the DEN/PB model group. (b) Western blot assay of PCNA and the quantitative results obtained by measuring the optical density of each band and expressed as the ratio of each targeted protein and beta-actin. Average values of 3 separate experiments along with the standard deviations are shown. ##P < 0.01 compared with the control group; *P < 0.05 compared with the DEN/PB model group.
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fig6: Expression of PCNA in the control and experimental groups at week 20. (a) Representative microscopic pictures of PCNA-stained liver sections by immunohistochemical analysis (100×) and quantification of the immunostained section of PCNA. ##P < 0.01 compared with the control group; *P < 0.05, **P < 0.01 compared with the DEN/PB model group. (b) Western blot assay of PCNA and the quantitative results obtained by measuring the optical density of each band and expressed as the ratio of each targeted protein and beta-actin. Average values of 3 separate experiments along with the standard deviations are shown. ##P < 0.01 compared with the control group; *P < 0.05 compared with the DEN/PB model group.

Mentions: Figure 6 reveals the immunohistochemical and Western blot analysis of PCNA. In immunohistochemical analysis (Figure 6(a)), the liver sections of the control mice stained for PCNA showed few nuclear-positive cells. However, DEN/PB treatment remarkably increased not only the intensity of immunostaining but also the number of PCNA-positive hepatocytes, which were both significantly reduced with bicyclol pretreatment. In the Western blot assay, preadministered bicyclol also decreased the increased expression of PCNA induced by DEN/PB (Figure 6(b)).


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)

Expression of PCNA in the control and experimental groups at week 20. (a) Representative microscopic pictures of PCNA-stained liver sections by immunohistochemical analysis (100×) and quantification of the immunostained section of PCNA. ##P < 0.01 compared with the control group; *P < 0.05, **P < 0.01 compared with the DEN/PB model group. (b) Western blot assay of PCNA and the quantitative results obtained by measuring the optical density of each band and expressed as the ratio of each targeted protein and beta-actin. Average values of 3 separate experiments along with the standard deviations are shown. ##P < 0.01 compared with the control group; *P < 0.05 compared with the DEN/PB model group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Expression of PCNA in the control and experimental groups at week 20. (a) Representative microscopic pictures of PCNA-stained liver sections by immunohistochemical analysis (100×) and quantification of the immunostained section of PCNA. ##P < 0.01 compared with the control group; *P < 0.05, **P < 0.01 compared with the DEN/PB model group. (b) Western blot assay of PCNA and the quantitative results obtained by measuring the optical density of each band and expressed as the ratio of each targeted protein and beta-actin. Average values of 3 separate experiments along with the standard deviations are shown. ##P < 0.01 compared with the control group; *P < 0.05 compared with the DEN/PB model group.
Mentions: Figure 6 reveals the immunohistochemical and Western blot analysis of PCNA. In immunohistochemical analysis (Figure 6(a)), the liver sections of the control mice stained for PCNA showed few nuclear-positive cells. However, DEN/PB treatment remarkably increased not only the intensity of immunostaining but also the number of PCNA-positive hepatocytes, which were both significantly reduced with bicyclol pretreatment. In the Western blot assay, preadministered bicyclol also decreased the increased expression of PCNA induced by DEN/PB (Figure 6(b)).

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