Chemically Induced Hepatocellular Carcinoma and Stages of Development with Biochemical and Genetic Modulation: A Special Reference to Insulin-Like-Growth Factor II and Raf Gene Signaling

Mukherjee, Biswajit; Ghosh, Manosij; Hossain, Chowdhury Mobaswar

doi:10.5772/28275

Cited by 5 publications

(2 citation statements)

References 28 publications

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“…It is a multistep process that includes initiation, promotion, and progression. 29 In this study, the initiation process, the exposure to the initiator DEN, probably causes DNA mutations in hepatocytes that transform normal cells into cancer cells. 30 DEN is a widely accepted and commonly used initiator of liver carcinogenesis in rats.…”

Section: Discussionmentioning

confidence: 95%

Therapeutic efficacy of a Dioscorea membranacea extract in a rat model of hepatocellular carcinoma: Histopathological aspects

Kerdput

Nilbu-Nga

Kaewnoonual

et al. 2021

Journal of Traditional and Complementary Medicine

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Hepatocellular carcinoma (HCC) is most common in adults and has a high mortality rate because of a lack of effective treatment options. We investigated the effect of a medicinal plant as a potential source of drugs against HCC. The rhizomes of Dioscorea membranacea Pierre (DM), Hua-Khao-Yen in Thai, are commonly used as ingredients for alternative treatment of cancer in Thailand. In this study, the anticancer effects of DM extract in HCC-bearing rats were evaluated with respect to gross morphology, histopathology, and leakage of liver enzymes. In untreated HCCs, typical features of liver cancer, including hepatic nodules, thick-cell cords, and pseudoglandular cell arrangements, were observed. In addition, the HCCs showed abnormal reticulin patterns and a high glypican3 expression. In HCC-bearing rats treated with DM the cancer areas and reticulin expression were significantly reduced compared to the untreated group ( p < 0.01). Sorafenib, the standard drug to treat HCC, reduced the cancer area further, but increased leakage of liver enzymes and decreased serum albumin concentration, indicating liver toxicity. These findings suggest that DM has an anticancer effect on HCCs in an animal model in vivo with potentially less severe side effects than sorafenib. Therefore, further studies of DM’s mechanism of action in HCC should be carried out.

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Section: Discussionmentioning

confidence: 95%

Therapeutic efficacy of a Dioscorea membranacea extract in a rat model of hepatocellular carcinoma: Histopathological aspects

Kerdput

Nilbu-Nga

Kaewnoonual

et al. 2021

Journal of Traditional and Complementary Medicine

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show abstract

“…The major avoidable causes of cancer are smoking, dietary imbalances, chronic infections and hormonal factors which are influenced primarily by lifestyle, other causal factors in human cancer are excessive sun exposure, viruses (such as human papilloma virus and cervical cancer) and pharmaceuticals (such as phenacetin, some chemotherapy agents, diethylstilbestrol, and estrogen) (Gold et al, 2002). Many hepatocarcinogens such as aflatoxins, acetylaminofluorene3 and diethylnitrosamine have been successfully used to develop hepatocarcinogenesis in animals (Mukherjee et al, 2009). Diethyl nitrosamine (DEN) is a potent hepatocarcinogenic nitrosamine, present in cheddar cheese, cured and fried meals, alcoholic beverages, cosmetics, agricultural chemicals and pharmaceutical agents, ground water having high level of nitrate (Mahmoud and Abdul-Hamid, 2012).…”

Section: Introductionmentioning

confidence: 99%

Moringa olifera Attenuated Nitrosodiethylamine-Induced Hepatocarcinogenesis by Modulating the Metabolic Activation and Detoxification Enzymes

Hussein

Abdel-Aal

Mady

2018

Benha Veterinary Medical Journal

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Moringa olifera was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and anticancer activity. This study was done to investigate the protective effects of moringa olifera on Diethylnitrosamine (DEN) induced Hepatocellular carcinoma in rats. Fourty five male albino rats were divided into three groups. Group (normal control group): rats administered distilled water only. Group II: rats received diethylnitrosoamine (200 mg/kg b.wt/i.p), two weeks later rats received (2 ml/kg b.wt) Carbon tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and CCl4 injections were repeated once again after 1 month from first DEN injection. Group III: rats received DEN then treated with moringa at a dose level of (500 mg/kg b.wt/orally) dissolved in distilled water for 6 weeks. All animals were sacrificed after the end of experiment. DEN induced HCC showed significant increase in hepatic marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease in serum albumin concentration. Also, the results of molecular analysis of liver tissue revealed significant upregulation in TNF-α gene expression level. Conversely, down-regulation in tumor suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with moringa olifera to DEN induced HCC protects the liver cells from damage by regulating the biochemical parameters. These findings suggest the potential efficacy of moringa as an additional chemopreventive agent in treatment of hepatocellular carcionoma via initiation of tumor suppressor gene (P53) and modulating the metabolic activation of detoxification Enzyme (cytochrome P450 2E1) and antiinflammatory effect.

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Macrolide antibiotics differentially influence human HepG2 cytotoxicity and modulate intrinsic/extrinsic apoptotic pathways in rat hepatocellular carcinoma model

Abdel-Hamid

El-Azab

Moustafa

2017

Naunyn-Schmiedeberg's Arch Pharmacol

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This study was designed to examine the potential antitumor effect of some macrolides: clarithromycin, azithromycin, and erythromycin on chemically induced hepatocellular carcinoma (HCC) in rats and on human hepatoma cells (HepG2) as well. The possible underlying antiapoptotic mechanisms were investigated. Antiproliferative activity was assessed in HepG2 using Sulforhodamine-B staining method. In vivo, HCC was induced in rats by initiation-selection-promotion protocol using diethylnitrosamine (200 mg/kg, single i.p. injection)/2-acetylaminofluorene (0.03% w/w supplemented-diet for 2 weeks)/carbon tetrachloride (2 ml/kg diluted in corn oil 1:1, single intra-gastric dose)/phenobarbitone sodium (0.05% w/w supplemented-diet for 28 weeks). Macrolides were administered once daily starting from the 3rd week until the 17th week at a dose of 100 mg/kg in the current 33-week study period. Clarithromycin showed a higher efficacy in the suppression of HepG2 proliferation with lower IC50 value than doxorubicin. In vivo, chemically-induced HCC rat model proved that clarithromycin suppressed HCC via induction of apoptosis through up-regulation of both extrinsic/intrinsic apoptotic pathways' proteins (TNFR1, cleaved caspase-3, and Bax with an increased Bax/Bcl-2 ratio) along with MMP-9 normalization. Similarly, azithromycin demonstrated antitumorigenic effect through both apoptotic pathways, however, to a lesser extent compared to clarithromycin. Moreover, azithromycin suppressed the proliferation of HepG2, however, at a higher IC50 than doxorubicin. Surprisingly, erythromycin increased HepG2 proliferation in vitro, along with worsened tumorigenic effect of the carcinogenic agents in the in vivo study with ineffective apoptotic outcome. Some macrolides represent potential antitumor agents; however, this evident anticancer activity is an individual effect rather than a group effect and involves modulation of both intrinsic and extrinsic apoptotic pathways.

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Chemically Induced Hepatocellular Carcinoma and Stages of Development with Biochemical and Genetic Modulation: A Special Reference to Insulin-Like-Growth Factor II and Raf Gene Signaling

Cited by 5 publications

References 28 publications

Therapeutic efficacy of a Dioscorea membranacea extract in a rat model of hepatocellular carcinoma: Histopathological aspects

Therapeutic efficacy of a Dioscorea membranacea extract in a rat model of hepatocellular carcinoma: Histopathological aspects

Moringa olifera Attenuated Nitrosodiethylamine-Induced Hepatocarcinogenesis by Modulating the Metabolic Activation and Detoxification Enzymes

Macrolide antibiotics differentially influence human HepG2 cytotoxicity and modulate intrinsic/extrinsic apoptotic pathways in rat hepatocellular carcinoma model

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