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

HepG2 human hepatoma cells were incubated for 24 or 48 h with various concentrations of YHK solution. After 24 h incubation, cell proliferation and cytotoxicity were determined by 3-(4,5-dimethylthiazol-2- yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium (MTT) assay. Cytotoxicity or necrosis was expressed as lactate dehydrogenase (LDH) release. After exponential growth phase HepG2 cells were treated with different doses of YHK and apoptosis was assessed by using an Annexin V-FITC kit. Further, oxidative stress was measured by dichlorofluorescein-diacetate (DCFH-DA) assay. As compared to control, YHK-treated cultures showed a significant time-course decrease of the proliferation rate of HepG2 cell growth (p < 0.01). This is likely to be due to an enhanced cytotoxicity (MTT and LDH tests) (p < 0.001). On the other hand, YHK showed in vitro to significantly enhance the oxidative stress of HepG2 cell (p < 0.01) while also markedly increasing apoptosis at 72 h with cells G2/M phase arrest (p < 0.01). These data suggest that YHK seem to modulate the extrinsic and intrinsic regulators of apoptosis and sensitize tumour cells to apoptosis. These preliminary data are worth interest when considering that this nutraceutical has been shown in vitro and in vivo to exert protective anti-tumour effect by redox statusmodulating and immuno-regulatory actions. Given its lack of toxicity so far reported, such natural product might represent an effective nutritional supplement in a number of pathological conditions where a chemopreventive strategy is planned.
 ...
PMID:In vitro study on the mechanisms of action of a novel phytotherapeutic compound against human hepatoma cells. 1751 35

In this study, we investigated the protective effect of macelignan, isolated from Myristica fragrans Houtt. (nutmeg) against tert-butylhydroperoxide (t-BHP)-induced cytotoxicity in a human hepatoma cell line, HepG2. The tetrazolium dye colorimetric test (MTT test) and lactate dehydrogenase (LDH) assay were used to monitor cell viability and necrosis, respectively. Lipid peroxidation [malondialdehyde (MDA) formation] was estimated by the fluorometric method. Intracellular reactive oxygen species (ROS) formation was measured using a fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA), and DNA damage was detected using single cell gel electrophoresis (comet assay). The results showed that macelignan significantly reduced the cell growth inhibition and necrosis caused by t-BHP. Furthermore, macelignan ameliorated lipid peroxidation as demonstrated by a reduction in MDA formation in a dose-dependent manner. It was also found that macelignan reduced intracellular ROS formation and DNA damaging effect caused by t-BHP. These results strongly suggest that macelignan has significant protective ability against oxidative damage caused by reactive intermediates.
 ...
PMID:Macelignan protects HepG2 cells against tert-butylhydroperoxide-induced oxidative damage. 1761 Dec 89

The chemoprotective effect of hydroxytyrosol (HT) against Sudan I-induced genotoxicity was investigated in a human hepatoma cell line, HepG2. The comet assay and micronucleus (MN) assay were used to monitor genotoxicity. Intracellular reactive oxygen species (ROS) formation was measured using a fluorescent probe, 2,7-dichlorofluorescein diacetate (DCFH-DA). The levels of oxidative DNA damage and lipid peroxidation were estimated by immunocytochemistry analysis of 8-hydroxydeoxyguanosine (8-OHdG) and by measuring levels of thiobarbituric acid-reactive substances (TBARS), respectively. Intracellular glutathione (GSH) level was estimated by fluorometric methods. The results showed that HT significantly reduced the genotoxicity caused by Sudan I. Furthermore, HT ameliorated lipid pexidation as demonstrated by a reduction in TBARS formation and attenuated GSH depletion in a concentration-dependent manner. It was also found that HT reduced intracellular ROS formation and 8-OHdG level caused by Sudan I. These results strongly suggest that HT has significant protective ability against Sudan I-induced genotoxicity.
 ...
PMID:Inhibition of Sudan I genotoxicity in human liver-derived HepG2 cells by the antioxidant hydroxytyrosol. 1829 12

Hydroquinone (HQ) is used as an antioxidant in rubber industry and as a developing agent in photography. HQ is also an intermediate in the manufacture of rubber, food antioxidant and monomer inhibitor. However, the mechanisms of the effects, in particular those related to its genotoxicity in humans, are not well understood. The aim of this study was to assess the genotoxic effects of HQ and to identify and clarify the mechanisms, using human hepatoma HepG2 cells. DNA strand breaks and DNA-protein crosslinks (DPC) were measured by the proteinase K-modified alkaline single cell gel electrophoresis (SCGE) assays. Using the SCGE assay, a significant dose-dependent increment in DNA migration was detected at concentrations of HQ (6.25-25 microM); but at the higher tested concentrations (50 microM), a reduction in the migration compared to the maximum migration at 25 microM was observed. Post-incubation with proteinase K significantly increased DNA migration in cells exposed to higher concentrations of HQ (50 microM). A significant increase of the frequency of micronuclei was found in the range from 12.5 to 50 microM in the micronucleus test (MNT). The data suggested that HQ caused DNA strand breaks, DPC and chromosome breaks. To elucidate the oxidative DNA damage mechanism, the 2,7-dichlorofluorescein diacetate (DCFH-DA) and o-phthalaldehyde (OPT) were chosen to monitor the levels of reactive oxygen species (ROS) and glutathione (GSH), respectively. The present study showed that HQ induced the increased levels of ROS and depletion of GSH in HepG2 cells, the doses being 25-50 and 6.25-50 microM, respectively. Moreover, HQ significantly caused 8-hydroxydeoxyguanosine (8-OHdG) formation in HepG2 cells at concentrations from 12.5 to 50 microM. All these results demonstrate that HQ exerts genotoxic effects in HepG2 cells, probably through DNA damage by oxidative stress. GSH, as a main intracellular antioxidant, is responsible for cellular defense against HQ-induced DNA damage.
 ...
PMID:Hydroquinone-induced genotoxicity and oxidative DNA damage in HepG2 cells. 1835 59

Under some conditions ibuprofen was either cytotoxic or cytostatic to rainbow trout cell lines: RTL-W1 (liver) and RTH-149 (hepatoma). Ibuprofen at up to 15 microg/mL was not cytotoxic, regardless of dosing protocols, exposure conditions, viability endpoints, or cell lines. Responses to higher ibuprofen concentrations depended on the test methodology. No cytotoxicity was seen when stock ibuprofen solutions had been prepared in ethanol. For stock solutions in dimethylsulfoxide (DMSO), ibuprofen from 50 to 1500 microg/mL elicited little cytotoxicity in cultures in which the final DMSO concentration was 0.05% (v/v), but was consistently cytotoxic after 24 h for cultures with 0.5% DMSO (v/v). Cytotoxicity was evaluated with alamar Blue (AB) and carboxyfluoroscein diacetate acetoxymethyl ester (CFDA-AM) as measures respectively of metabolic activity and membrane integrity. Effective concentrations (EC50s) for ibuprofen with AB and CFDA-AM depended on whether the stock solution was dosed directly into a culture well or mixed in medium prior to being added to a well. For indirect dosing, ibuprofen was more cytotoxic in medium without fetal bovine serum (FBS), whereas for direct dosing ibuprofen was equally cytotoxic in medium with or without FBS. As judged by AB and CFDA-AM EC50s, dosing ibuprofen was directly 10 to 30 times more cytotoxic. In FBS-containing cultures, which was dosed with increasing ibuprofen and DMSO at 0.05% (v/v), cell proliferation was impaired at 50 and 150 microg/mL ibuprofen. Lipopolysaccharide (LPS) at 50 microg/mL had little influence on these cytotoxic and cytostatic effects of ibuprofen in medium with FBS.
 ...
PMID:Effects of ibuprofen on the viability and proliferation of rainbow trout liver cell lines and potential problems and interactions in effects assessment. 1856 1

The chemoprotective effect of hydroxytyrosol (HT), a strong antioxidant compound from extra virgin olive oil, against acrylamide (AA)-induced genotoxicity was investigated in a human hepatoma cell line, HepG2. The micronucleus test (MNT) assay was used to monitor genotoxicity. In MNT, we found that HT at all tested concentrations (12.5-50 microM) significantly reduced the micronuclei frequencies in a concentration-dependent manner caused by AA. In order to clarify the underlying mechanisms we measured the intracellular reactive oxygen species (ROS) formation using 2,7-dichlorofluorescein diacetate (DCFH-DA) as a fluorescent probe. Intracellular glutathione (GSH) level was estimated by fluorometric methods. The rate-limiting enzyme in GSH synthesis is gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-GCS was measured using Western blotting. The results showed that HT significantly concentration-dependent reduced the genotoxicity caused by AA. Furthermore, HT was able to reduce intracellular ROS formation and attenuate GSH depletion caused by AA in a concentration-dependent manner. It was also found that HT enhanced the expression of gamma-GCS in HepG2 cells treated with 10 mM AA using immunoblotting in a concentration-dependent manner. The results showed that HT reduced the AA-induced genotoxicity by decreasing the ROS level and increasing the GSH level. The data strongly suggest that HT have significant protective ability against AA-induced genotoxicity in vitro.
 ...
PMID:Inhibition of acrylamide genotoxicity in human liver-derived HepG2 cells by the antioxidant hydroxytyrosol. 1876 36

Tumor cells are known to produce larger amounts of reactive oxygen species (ROS) than normal cells. Although numerous reports have indicated the importance of ROS in urokinase plasminogen activator (uPA) production, the precise mechanisms remain controversial. In our study, we investigated the effect of ROS on uPA generation in human hepatoma cells, HepG2 and Hep 3B. We determined the effects of hepatocyte growth factor (HGF) on the regulation of ROS, which resulted in suppression of ROS production, as measured with the fluorescent probe, 2'-7'-dichlorofluorescein diacetate. The role of HGF in modulating ROS production, particularly that regulated by Rac-1, was determined. HGF suppressed the increment in Rac-1-regulated ROS in both cell lines. Treatment with 200 micrometer of H(2)O(2) showed a 1.6-2.1 fold increment in HGF, but a little increment occurred at 500 micrometer of H(2)O(2). It looks no dose dependent manner. Combined treatment with H(2)O(2) and HGF, resulted in a slightly increased production of HGF compared to no treatment (control). Also, H(2)O(2) upregulated uPA expression in both hepatoma cell lines. To identify the downstream pathways regulated by ROS, we treated cells with PD 98059, an MEK inhibitor, and SB 203580, a p38 inhibitor, after treatment with H(2)O(2), and showed negative control between ERK and p38 kinase activities for uPA regulation. We found that HGF modulate Rac-1-regulated ROS production through activation of Akt and ROS regulates uPA production via MAP kinase, which provides a novel clue to clarify the mechanism underlying hepatoma progression.
 ...
PMID:Reactive oxygen species regulate the generation of urokinase plasminogen activator in human hepatoma cells via MAPK pathways after treatment with hepatocyte growth factor. 1929 37

The aim of this work was to determine the effect of vitamin C, diallyl disulfide (DADS) and dipropyl disulfide (DPDS) towards N-nitrosopiperidine (NPIP) and N-nitrosodibutylamine (NDBA)-induced apoptosis in human leukemia (HL-60) and hepatoma (HepG2) cell lines using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. None of the vitamin C (5-50 microm), DADS and DPDS (1-5 microm) concentrations selected induced a significant percentage of apoptosis. In simultaneous treatments, vitamin C, DADS and DPDS reduced the apoptosis induced by NPIP and NDBA in HL-60 and HepG2 cells (around 70% of reduction). We also investigated its scavenging activities towards reactive oxygen species (ROS) produced by NPIP and NDBA using 2',7'-dichlorodihydrofluorescein diacetate in both cell lines. ROS production induced by both N-nitrosamine was reduced to control levels by vitamin C (5-50 microm) in a dose-dependent manner. However, DADS (5 microm) increased ROS levels induced by NPIP and NDBA in HL-60 (40 and 20% increase, respectively) and HepG2 cells (18% increase), whereas DPDS was more efficient scavenger of ROS at the lowest concentration (1 microm) in both HL-60 (52 and 25% reduction, respectively) and HepG2 cells (24% reduction). The data demonstrated that the scavenging ability of vitamin C and DPDS could contribute to inhibition of the NPIP- and NDBA-induced apoptosis. However, more than one mechanism, such as inhibition of phase I and/or induction of phase II enzymes, could be implicated in the protective effect of dietary antioxidants towards NPIP- and NDBA-induced apoptosis in HL-60 and HepG2 cells.
 ...
PMID:Antiapoptotic effects of dietary antioxidants towards N-nitrosopiperidine and N-nitrosodibutylamine-induced apoptosis in HL-60 and HepG2 cells. 1930 Dec 45

The chemoprotective effect of hydroxytyrosol (HT) against acrylamide (AA)-induced cytotoxicity and DNA damage was investigated in a human hepatoma cell line, HepG2. The cytotoxicity was estimated by methyl thiazol tetrazolium bromide (MTT) assay. The comet assay was used to monitor DNA damage. The intracellular reactive oxygen species (ROS) formation and the level of oxidative DNA damage were estimated by using 2,7-dichlorofluorescein diacetate (DCFH-DA) as a fluorescent probe and by using immunocytochemistry analysis of 8-hydroxydeoxyguanosine (8-OHdG). Intracellular glutathione (GSH) level was estimated by fluorometric methods. The results showed that HT significantly reduced the cytotoxicity, DNA damage, intracellular ROS formation and 8-OHdG level caused by AA in a concentration-dependent manner. It was also found that HT concentration-dependently attenuated GSH depletion in HepG2 cells treated with 10mM AA. These findings suggest that HT has a strong protective ability against the cytotoxicity and DNA damage caused by AA.
 ...
PMID:Protective effect of hydroxytyrosol against acrylamide-induced cytotoxicity and DNA damage in HepG2 cells. 1942 82

Deoxynivalenol (DON) is a trichothecene mycotoxin and a cereals contamination, whose cytotoxicity has been shown in animals and various cells. However, with respect to the deoxynivalenol-induced DNA damage, especially in humans, are not well understood. The aim of this study was to assess the role of oxidative stress in deoxynivalenol-induced DNA damage, using human hepatoma HepG2 cells. Exposure of the cells to DON caused significant increase of DNA migration in comet assay at concentrations of 3.75-30 microM, which suggests that DON caused DNA strand breaks. To elucidate the role of antioxidation in those effects, DNA migration was monitored by pre-treatment with hydroxytyrosol (HT) as an antioxidant in comet assay. It was found that DNA migration with pre-treatment of HT was dramatically decreased. The DNA damage induced by DON was almost completely prevented. In order to clarify the underlying mechanisms, we evaluated the level of reactive oxygen species (ROS) production with the 2,7-dichlorofluorescein diacetate (DCFH-DA) assay. Significant increase in the level of ROS was observed in HepG2 cells at a higher concentration (60 microM). The involvement of lipid peroxidation in the DNA damage of DON was confirmed by using immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG) and by measuring levels of thiobarbituric acid-reactive substances (TBARS), the doses being 7.5-60 microM and 3.75-15 microM, respectively. These results indicate that the DNA damage induced by DON in HepG2 cells is probably related to the oxidative stress.
 ...
PMID:The role of oxidative stress in deoxynivalenol-induced DNA damage in HepG2 cells. 1948 9


<< Previous 1 2 3 4 5 6 7 8 9 Next >>