Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present paper, we report the effect of a grape seed procyanidin extract (GSPE) on antioxidant enzyme systems (AOEs). Gene expression was tested using the hepatocarcinoma cell line HepG2 by exposing it to several GSPE doses between 0 and 100 mg/L for 24 h. We evaluated mRNA expression and enzyme activity levels using real time RT-PCR and spectrophotometry. The results suggested a transcriptional GSPE regulation of glutathione related enzymes caused by an increase both in mRNA and in enzyme activity levels overall at 15 mg/L. We also assessed the GSPE effect on AOEs in cells submitted to oxidative stress. Under oxidative conditions (1 mM H(2)O(2), 1 h), we found a decrease in GSH content and an increase in MDA, and we suggested a posttranslational regulation of GPx/GR mRNAs and a transcriptional enhancement of GST mRNA. The GSPE pretreatment (15 mg/L, 23 h) before HepG2 submission to H(2)O(2) (1 mM, 1 h) showed an increase of the mRNA of GPx/GR with respect to the H(2)O(2) group, whereas the GSH content was similar to the control group. However, the GPx/GR enzyme activities were not increased. We hypothesize that GSPE probably improves the cellular redox status via glutathione synthesis pathways instead of regulation of the GPx and/or GR activities protecting against oxidative damage.
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PMID:Grape seed procyanidins prevent oxidative injury by modulating the expression of antioxidant enzyme systems. 1602 99

Thioredoxin reductase (TrxR) in conjunction with thioredoxin (Trx) is a ubiquitous intracellular oxidoreductase system with antioxidant and redox regulatory roles. In some human tumors, the thioredoxin system is found overexpressed. We have used an antisense approach to investigate whether inhibition of TrxR overexpression can suppress the growth of human hepatocellular carcinoma SMMC-7721 cells. TrxR cDNA fragment was inserted in the antisense direction into pcDNA3.1/myc-His and SMMC-7721 cells were stably transfected with the plasmid construct. The results showed that TrxR antisense RNA could significantly reduce TrxR mRNA level and activity, and suppress the growth of SMMC-7721 cells. Cell-cycle analysis showed G2/M phase arrest in SMMC-7721 cells transfected with TrxR antisense plasmid. TrxR antisense RNA could significantly increase p53 mRNA level and decrease Bcl-2 mRNA level by reverse transcriptase-polymerase chain reaction (RT-PCR). Furthermore a significant decrease in human telomerase reverse transcriptase (hTERT) mRNA level was found in SMMC-7721 cells transfected with TrxR antisense plasmid. Flow cytometry and telomere fluorescence in situ hybridization (Flow FISH) showed that TrxR antisense RNA could significantly reduce the telomere fluorescence in SMMC-7721 cells. The results suggested that TrxR antisene RNA inhibited the growth of SMMC-7721 cells through an accumulation of cell cycle at G2/M phase, an increase in p53 mRNA level and a reduction in telomere fluorescence and Bcl-2, hTERT mRNA levels.
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PMID:Inhibitory effects of thioredoxin reductase antisense RNA on the growth of human hepatocellular carcinoma cells. 1608 46

Allelic losses on chromosome 1p are frequent in hepatocellular carcinoma (HCC), suggesting the presence of a tumour suppressor gene in this region. The gene for peroxiredoxin 1 (PRDX1), an antioxidant enzyme, has been mapped to 1p34.1. Mice lacking PRDX1 develop HCC with high frequency. Because oxidative stress has been implicated in the pathogenesis of HCC, this study was designed to determine whether the PRDX1 gene is mutated in human HCC using loss of heterozygosity (LOH) analysis, polymerase chain reaction/denaturing gradient gel electrophoresis, and DNA sequencing. LOH of at least one of four microsatellite markers within 0.8 Mb of the PRDX1 gene was seen in three of 34 informative HCCs, but no mutations or polymorphisms in the translated exons 2-6 of the PRDX1 gene were found. These results suggest that genetic alterations of the PRDX1 locus are rare events in human HCC, indicating that other genes on chromosome 1p contribute to liver carcinogenesis.
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PMID:Rare allelic imbalances, but no mutations of the PRDX1 gene in human hepatocellular carcinomas. 1625 21

The present investigation was carried out to evaluate the antioxidant nature of ethanolic extract of Terminalia arjuna bark (EETA) on N-nitrosodiethylamine (DEN) induced liver cancer in male Wistar albino rats. Liver cancer was induced by single intraperitonial injection of DEN (200 mg/kg). After 2 weeks of DEN administration, Phenobarbital (PB) was given to promote the cancer for up to 14 successive weeks. EETA extract (400 mg/kg) was given post-orally for 28 days to hepatocellular carcinoma-bearing rats. After the experimental period, all the animals were sacrificed and serum, liver and kidney samples were collected for further biochemical analysis. The levels of lipid peroxides (LPO) under basal and also in the presence of inducers (H(2)O(2), ascorbate and FeSO(4)) were estimated in serum, liver and kidney of control and experimental animals. Enzymic antioxidants, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-enzymic antioxidants like Vitamin C (Vit-C) and Vitamin E (Vit-E) levels were determined in all the groups of animals. A significant increase in LPO levels were observed while the levels of enzymic and non-enzymic antioxidants were decreased, when subjected to DEN induction. These altered enzyme levels were ameliorated significantly by administration of EETA at the concentration of 400 mg/kg in drug-treated animals. This protective effect of EETA was associated with inhibition of LPO induced by DEN and to maintain the antioxidant enzyme levels. Our results show an antioxidant activity of T. arjuna bark against DEN-induced liver cancer.
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PMID:Antioxidant activity of Terminalia arjuna bark extract on N-nitrosodiethylamine induced hepatocellular carcinoma in rats. 1632 60

Oxidative stress, including the generation of reactive oxygen species (ROS), is known to be involved in apoptosis. Preventing apoptosis may thereby induce a malignant transformation of liver tumor cells. Estradiol (E2) is a potent endogenous antioxidant. We examined the proapoptotic role of progesterone as well as the antiapoptotic role of E2 in human hepatoma HuH-7 cells in a state of early apoptosis induced by tumor necrosis factor (TNF) alpha. The TNF alpha-induced ROS generation, lipid peroxidation, antioxidant enzyme consumption, a proapoptotic predominant expression of Bcl-2 family proteins, and a disruption of mitochondrial membrane potential were all inhibited by E2, and then they were further stimulated by progesterone in HuH-7 cells. The inhibitory effects of E2 were blocked by coincubation with progesterone. Treatment with the progesterone receptor antagonist RU486 led to the blockage of the progesterone-mediated responses to E2 pretreatment in TNF alpha-induced apoptosis. These findings demonstrate that E2 inhibits the TNF alpha-induced early apoptosis in hepatoma cells, by suppressing the oxidative stress processes, whereas progesterone acts in a manner opposite from the effects of E2, and the inhibitory effects of E2 were blocked by progesterone, thus leading to the apoptosis of hepatoma cells.
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PMID:Effects of estradiol and progesterone on tumor necrosis factor alpha-induced apoptosis in human hepatoma HuH-7 cells. 1686 Aug 28

To identify potential biomarkers for the monitoring and risk assessment of benzo[a]pyrene (BaP), the oxidative stress-related DNA damage and p53 modification were investigated in human hepatoma HepG2 cells. Benzo[a]pyrene exposure induced a decrease in the cell viability, but increased the antioxidant enzyme activity as well as the DNA and lipid damage. The p53 protein activation appeared to have been a downstream response to the benzo[a]pyrene-induced DNA damage, suggesting p53 plays important roles in the defense against benzo[a]pyrene-induced genotoxicity. The response of phosphorylated p53 may be more sensitive towards benzo[a]pyrene exposure than normal p53. Following DNA damage, the activation of p53 acts as a transcriptional regulator of several target genes, including, p21 protein; a gene that encodes the Cdk inhibitor and is induced by exposure to benzo[a]pyrene. The p53 mRNA level was increased after the treatment of cells with benzo[a]pyrene, as well as following the induction of p53 protein, suggesting the benzo[a]pyrene-stimulated p53 accumulation may also be transcriptionally induced. The overall results suggest that benzo[a]pyrene leads to serious DNA damage, which leads to the transcription of the p53 gene; that the subsequent p53 protein accumulation up-regulates the cellular p21 protein. Oxidative DNA damage and p53 accumulation seem to be related to benzo[a]pyrene toxicity; however, their potential as biomarkers in environmental monitoring and risk assessment needs to be validated in the context of their specificity and sensitivity.
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PMID:Benzo[a]pyrene-induced DNA damage and p53 modulation in human hepatoma HepG2 cells for the identification of potential biomarkers for PAH monitoring and risk assessment. 1702 27

Cyclophosphamide (CTX) is in the nitrogen mustard group of alkylating antineoplastic chemotherapeutic agents. It is one of the most frequently used antitumor agents for the treatment of a broad spectrum of human cancers. Thioredoxin reductase (TrxR) catalyze the NADPH-dependent reduction of thioredoxin and play an important role in multiple cellular events related to carcinogenesis including cell proliferation, apoptosis, and cell signaling. This enzyme represents a promising target for the development of cytostatic agents. The purpose of this study is to determine whether CTX could target TrxR in vivo. Lewis lung carcinoma and solid H22 hepatoma treated with 50-250 mg/kg CTX for 3 h lost TrxR activity in a dose-dependent fashion. Over 75% and 95% of TrxR activity was lost at the dose of 250 mg/kg. There was, however, a recovery of TrxR activity such that it attained normal levels by 120 h after a dose of 250 mg/kg. In addition, we found that CTX caused a preferential TrxR inhibition over other antioxidant enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase. We also used ascites H22 cells to investigate cancer cells response after TrxR was inhibited by CTX in vivo since CTX is needed to be activated by liver cytochrome P450 enzymes. The time course and dose-dependent changes of cellular TrxR activity were similar with those in tumor tissue. CTX caused a dose-dependent cellular proliferation inhibition which was positively correlated with TrxR inhibition at 3 h. Furthermore, when 3 h CTX-treated cells with various TrxR backgrounds, harvested from ascites-bearing mice, were implanted into mice, the proliferations of these cells were again proportionally dependent on TrxR activity. The TrxR inhibition could thereby be considered as a crucial mechanism contributing to anticancer effect seen upon clinical use of CTX.
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PMID:Cyclophosphamide as a potent inhibitor of tumor thioredoxin reductase in vivo. 1715 7

Both selenium and green tea have been shown to have potential antitumor effects. Here we have investigated the anticarcinogenic effect of the selenium-enriched green tea extract (Se-TE) in a Kunming mice model transplanted with human hepatoma cells HepG2. Mice were assigned to 8 groups consisting of 10 mice each after tumor cell inoculation. The control group received only water, whereas the remaining groups received regular green tea extract (RT), Se-TE which was produced by fertilization with selenite on tea leaves, selenite, and RT + selenite. After the mice were fed intragastrically with these agents for 8 days, tumor growth in RT-, Se-TE-, and selenite-fed mice was significantly suppressed, compared with that in control mice (P < 0.001). Supplementation with Se-TEs and selenite was able to elevate mice blood and liver Se concentrations, but did not significantly enhance selenoprotein glutathione peroxidase and other antioxidant enzyme superoxide dismutase activity in mice blood and liver. These results suggest that the antitumor function of Se-TEs may be attributed to the oxidative stress induced by selenium and green tea components in a suitable selenium supplementation pathway.
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PMID:Anticarcinogenic activity of selenium-enriched green tea extracts in vivo. 1754 12

Thioredoxin reductase reduces thioredoxin, thereby contributing to multiple cellular events related to carcinogenesis including cell proliferation, apoptosis, and cell signaling. This selenium-containing oxidoreductase is over-expressed in many malignant cells and has been proposed as a target for cancer therapy. Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. The purpose of this study is to test the hypothesis that anticancer efficacy of ifosfamide may rely on its ability to inhibit thioredoxin reductase in tumor. To inspect the consequence of thioredoxin reductase inhibition by ifosfamide on tumor cell proliferation, mice bearing hepatoma 22 (H22) cells in ascites were injected with 350 mg/kg ifosfamide. Thioredoxin reductase activity was maximally inhibited by half at 6 h, and a subsequent pronounced cellular proliferation inhibition due to cell cycle arrest in G(1) phase was found. Moreover, at 6 h, except thioredoxin reductase inhibition, ifosfamide did not affect cell cycle or other measured antioxidant enzymes activity in the tumor cells. Intriguingly, when these cells were injected into healthy mice, they totally lost the capacity of causing either ascitic or solid tumors. Thioredoxin reductase inhibition could also be found in solid H22 tumor by 62%, bladder by 74% and kidney by 37% at 6 h. Overall, these observations provide direct evidence that inhibition of thioredoxin reductase activity in malignant cells by ifosfamide is highly associated with its anticancer effect and the mechanism of ifosfamide systemic toxicity may be related to multi-organ inhibition of thioredoxin reductase activity.
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PMID:Thioredoxin reductase inactivation as a pivotal mechanism of ifosfamide in cancer therapy. 1802 6

The reduced incidence of cancer that has been observed in Asian population traditionally consuming soy-based food has been linked to the antioxidant potential of soy isoflavones, in particular daidzein and genistein. The present study was undertaken in order to test the antioxidative potential of daidzein and to examine the effect of daidzein treatment on the expression of the antioxidant enzyme catalase in the human hepatoma cell lines Huh-7 and HepG2. Daidzein itself did not display radical scavenging activity but it significantly increased the activity of the antioxidant enzyme catalase. Huh-7 cells were much more susceptible to daidzein cytotoxicity than HepG2 cells and showed much lower basal activity in luciferase reporter gene assays with the 3.2 kb fragment of the human catalase promoter. However, treatment with daidzein at a non-toxic concentration resulted in a similar induction of promoter activity in both cell lines. Reporter gene studies with different promoter constructs in HepG2 cells restrict the potential localization of the main regulatory elements for basal and inducible activity of the catalase promoter to a region approximately 120 bp to 300 bp upstream of the start codon of the catalase gene. From our results, we conclude that in human hepatoma cells daidzein at a non-toxic concentration increases the activity of human catalase and induces the transcription of the catalase gene via interaction with the proximal part of the promoter.
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PMID:Increased expression of catalase in human hepatoma cells by the soy isoflavone, daidzein. 1804 76


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