In vitro anticancer activity of cardiospermum halicacabum (linn) against hepatocellular carcinoma cell line (hep-g2).

Cardiospermum halicacabum is important medicinal plant which belongs to Sapindaceae family.In present study, ethanolic leaf extract of Cardiospermum halicacabum was examined for its anticancer activity against Hepatocellular carcinoma cell line (Hep-G2) using MTT assay. The leaf extract shows significant cytotoxic effect with 90% of inhibition when compared to standard drug.

Cytotoxicity Studies Of An Ethnobotanically Selected Solanum Pubescens Willd. Against Selected Human Cancer Cell Lines

Objective: The present study was aimed to determine the cytotoxicity concentration (CTC50) of different extracts made from the leaf and stem bark of an ethno botanically selected S. pubescens against Human liver carcinoma (Hep G2), Human colon carcinoma (CaCo2) and Human breast cancer (T-47 D) cell lines. Methods: Ethnobotanical survey was done through interviewing traditional medicinal practitioners then a potential herbal plant was selected after a thorough literature survey and its identity was confirmed. The soxhlet extraction method was adopted using five different solvents from leaf and stem bark powders of the study plant and the CTC50 of all the extracts were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay method. Results: Among the different extracts, CTC50 values were significant for stem bark extracts made from methanol (24.51±0.08 µg/ml) against Hep G2, while leaf chloroform extract was promising (57.15±1.75 µg/ml) against CaCo2 and n-hexane extract of leaf exhibited significant value (20.27±1.52 µg/ml) against T-47 D cancer cell lines. Conclusion: The major findings of the present study clearly provides evidence that the leaf and stem bark of S. pubescens possesses the potential anticancer bioactive compound solasodine.

Content characteristics and cytotoxicity detection of silver ion products / 中华烧伤杂志

Objective@#To analyze the silver content, homogeneity, and cytotoxicity of silver-containing products.@*Methods@#(1) Five kinds of silver-containing products A, B, C, D, and E were purchased from the market, and products A, B, C, and D are liquid or gel form while product E was dressing form. The silver content of each product and the homogeneity of product E were determined by flame method. The sample number was 3. (2) Human hepatocellular carcinoma cell line (HepG2) was selected as the evaluation model. Four silver-containing products A, B, C, and D were diluted with high-glucose dulbecco′s modified eagle medium (DMEM) at multiple ratios of 1∶100, 1∶200, 1∶400, and 1∶800, and then they were used for cell culture. Cells cultured with high-glucose DMEM and high-glucose DMEM containing 20 μg/mL silver nitrate were used as blank control and positive control, respectively. The cell viability was determined by methyl thiazolyl tetrazolium assay, and each sample number was 5. (3) Four mass concentrations of 0.031 3, 0.062 5, 0.125 0, and 0.250 0 μg/mL were prepared from silver-containing product A, and then they were used to culture HepG2 cell. Cells cultured with high-glucose DMEM containing fetal calf serum and 294 μg/mL potassium dichromate were used as positive control, while those containing fetal calf serum were used as blank control. Hoechst 33258 staining method was used to detect apoptosis rate of cells. The tail moment, tail length, and the percentage of DNA in the tail of cells were observed by comet assay to evaluate DNA damage. The sample numbers were all 3. Data were processed with one-way analysis of variance and least significant difference-t test.@*Results@#The silver content of products A, B, C, and D was (256.5±1.5) μg/mL, (271.5±1.3) μg/mL, (652.4±2.6) μg/g , (330.0±2.1) μg/g, which was in accordance with labelled amount. The silver content of product E was (0.158±0.013) mg/g, and the silver content of each piece of product E was (0.125±0.017) mg/g, showing good uniformity of product E. (2) Compared with the rate of blank control, the cell survival rates of product A at the dilution ratio of 1∶100, product B at the dilution ratio of 1∶100, and product C at the dilution ratio of 1∶100 and 1∶200 were significantly reduced (t=35.506, 8.914, 37.594, 30.693, P<0.01). Compared with the rate of positive control, the cell survival rates of product A at the dilution ratio of 1∶200, 1∶400, and 1∶800, product C at the dilution ratio of 1∶400 and 1∶800, products B and D at each dilution ratio were increased significantly (t=27.537, 18.262, 18.709, 26.333, 41.762, 15.776, 19.759, 20.443, 15.715, 26.792, 24.963, 31.803, 30.537, P<0.01). (3) The apoptosis rates of cells treated by 0.250 0 μg/mL product A and positive control were (6.1±0.4)% and (62.2±3.9)% respectively, which were significantly higher than the apoptosis rate of blank control [(3.3±0.7)%, t=13.327, 30.475, P<0.05]. The apoptosis rates of cells treated by 0.031 3, 0.062 5, 0.125 0 μg/mL product A were (2.9±0.4)%, (3.1±0.4)%, and (4.2±0.9)% respectively, which were close to the apoptosis rate of blank control (t=1.181, 0.133, 1.097, P>0.05). (4) The tail moment, tail length, and tail DNA percentage of cells cultured with 0.125 0 and 0.250 0 μg/mL product A were significantly higher than those cultured with blank control (t=29.026, 51.194, 21.851, 36.138, 24.721, 50.455, P<0.05 or P<0.01). However, the tail moment, tail length, and tail DNA percentage of cells cultured with 0.031 3 and 0.062 5 μg/mL product A were close to those cultured with blank control (t=5.878, 3.429, 2.779, 1.960, 1.328, 7.763, P>0.05).@*Conclusions@#The silver content of silver-containing products meets the requirements of the labeling. The concentration of product C is higher than that of other products, leading to a greater possibility of decreasing the survival rate of HepG2 cells. It is suggested that the products A and B should be taken as reference in the concentration setting of silver ion products. The product solution with higher concentration may have higher risk of damage to cell DNA. Therefore, it is not recommended to upregulate silver content of relevant products blindly in order to achieve better antibacterial effect.

Mechanism of effective components of Mori Folium in alleviating insulin resistance based on JNK signaling pathway / 中国中药杂志

A stable hepatoma cell line(Hep G2 cell) insulin resistance model was established and used to analyze the effect of effective components of Mori Folium in alleviating insulin resistance,and preliminary explore the mechanism for alleviating insulin resistance. The Hep G2 insulin action concentration and the duration of action were investigated using the glucose oxidase method(GOD-POD method) to establish a stable Hep G2 insulin resistance model. Normal control group,model group,Mori Folium polysaccharide group,Mori Folium flavonoid group and rosiglitazone group were divided to determine the glucose consumption. The effect of Mori Folium effective components on Hep G2 insulin resistance was analyzed. The mRNA expressions of JNK,IRS-1 and PDX-1 in each group were detected by Real-time quantitative PCR(qRT-PCR). The protein expressions of p-JNK,IRS-1 and PDX-1 were detected by Western blot. And the mechanism of effective components of Mori Folium in alleviating insulin resistance was investigated. The results showed that the glucose consumption was significantly decreased in the insulin resistance cells after incubation with 25. 0 mg·L-1 insulin for 36 h(P<0. 01),and the model was relatively stable within 36 h. Mori Folium polysaccharides and flavonoids all alleviated insulin resistance,among which Mori Folium flavonoids had better effect in alleviating Hep G2 insulin resistance(P<0. 05). The qRT-PCR analysis showed that Mori Folium polysaccharides and flavonoids could inhibit JNK and IRS-1 mRNA expressions,while enhancing PDX-1 mRNA expression. Western blot analysis displayed that Mori Folium polysaccharides and flavonoids could inhibit p-JNK and IRS-1 protein expressions,while enhancing PDX-1 protein expression. Mori Folium polysaccharides and flavonoids can alleviate insulin resistance in Hep G2 cells,and its mechanism may be the alleviation of insulin resistance by inhibiting JNK signaling pathway.

Metabolites profiling and hypolipidemic/hypocholesterolemic effects of persimmon (Diosyros kaki Thumb.) by different processing procedures: in vitro and in vivo studies / 한국영양학회지

PURPOSE: Our previous study demonstrated that persimmon (Diospyros kaki Thumb.) at different stages of ripening provided different protective effects against high-fat/cholesterol diet (HFD)-induced dyslipidemia in rats. In this study, we compared the metabolites profile and gene expressions related to triglyceride (TG)/cholesterol metabolism in vitro and in vivo after treating with persimmon water extracts (PWE) or tannin-enriched persimmon concentrate (TEP). METHODS: Primary and secondary metabolites in test materials were determined by GC-TOF/MS, UHPLC-LTQ-ESI-IT-MS/MS, and UPLC-Q-TOF-MS. The expression of genes related to TG and cholesterol metabolism were determined by RT-PCR both in HepG2 cells stimulated by oleic acid/palmitic acid and in liver tissues obtained from Wistar rats fed with HFD and PWE at 0, 150, 300, and 600 mg/d (experiment I) or TEP at 0, 7, 14, and 28 mg/d (experiment II) by oral gavage for 9 weeks. RESULTS: PLS-DA analysis and heatmap analysis demonstrated significantly differential profiling of metabolites of PWE and TEP according to processing of persimmon powder. In vitro, TEP showed similar hypolipidemic effects as PWE, but significantly enhanced hypocholesterolemic effects compared to PWE in sterol regulatory element-binding protein 2 (SREBP2), HMG-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesterol 7α-hydroxylase (CYP7A1), and low density lipoprotein receptor (LDLR) gene expression. Consistently, TEP and PWE showed similar hypolipidemic capacity in vivo, but significantly enhanced hypocholesterolemic capacity in terms of SREBP2, HMGCR, and bile salt export pump (BSEP) gene expression. CONCLUSION: These results suggest that column extraction after hot water extraction may be a good strategy to enhance tannins and long-chain fatty acid amides, which might cause stimulation of hypocholesterolemic actions through downregulation of cholesterol biosynthesis gene expression and upregulation of LDL receptor gene expression.

Generation of Multilayered 3D Structures of HepG2 Cells Using a Bio-printing Technique

BACKGROUND/AIMS: Chronic liver disease is a major widespread cause of death, and whole liver transplantation is the only definitive treatment for patients with end-stage liver diseases. However, many problems, including donor shortage, surgical complications and cost, hinder their usage. Recently, tissue-engineering technology provided a potential breakthrough for solving these problems. Three-dimensional (3D) printing technology has been used to mimic tissues and organs suitable for transplantation, but applications for the liver have been rare. METHODS: A 3D bioprinting system was used to construct 3D printed hepatic structures using alginate. HepG2 cells were cultured on these 3D structures for 3 weeks and examined by fluorescence microscopy, histology and immunohistochemistry. The expression of liver-specific markers was quantified on days 1, 7, 14, and 21. RESULTS: The cells grew well on the alginate scaffold, and liver-specific gene expression increased. The cells grew more extensively in 3D culture than two-dimensional culture and exhibited better structural aspects of the liver, indicating that the 3D bioprinting method recapitulates the liver architecture. CONCLUSIONS: The 3D bioprinting of hepatic structures appears feasible. This technology may become a major tool and provide a bridge between basic science and the clinical challenges for regenerative medicine of the liver.

Inhibitory effect of epigallocatechin-3-gallate on the proliferation of hepatic carcinoma cells / 解放军医学杂志

Objective To study the effect of epigallocatechin-3-gallate (EGCG) on the proliferation and apoptosis of hepatic carcinoma HepG2 cells, and to explore the possible mechanism. Methods HepG2 cells were treated with EGCG in various concentrations (0, 25, 50, 100, 200, 400mg/L) for 24, 48 and 72h, and then the cell proliferation inhibition rate was determined with MTT. Again, the HepG2 cells were treated with various concentrations of EGCG (0, 50, 100, 200mg/L) for 24h, and then the cell apoptosis rate, cell cycle, and the expressions of cell division cycle protein 25A (CDC25A), and Smad3 protein were determined with flow cytometry. mRNA expressions of CDC25A and Smad3 were assessed with RT-PCR. Results The results of MTT showed that various concentrations of EGCG inhibited the growth of HepG2 cells in dose and time dependent manner (P<0.01). The result of flow cytometry showed that, with the increase of of EGCG concentration, the cell proliferation index (PI) decreased significantly (P<0.01), while the apoptosis rate increased obviously (P<0.01); the expression levels of CDC25A protein and mRNA decreased (P<0.05) and of Smad3 protein and mRNA increased (P<0.05). Conclusion EGCG may play a role in growth inhibition of hepatic carcinoma cells by down-regulating the expression of CDC25A, up-regulating the expression of Smad3, thus inhibiting proliferation and inducing apoptosis of HepG2 cells.

Confirmation of HIF-1α Independent Pathway in the Progression of HepG2 Cells by Hypoxic Condition

BACKGROUND/AIMS: When hepatocellular carcinoma (HCC) is exposed to hypoxic condition, HIF-1α is activated and results in angiogenesis and increased tumor burden. Although inhibition of HIF-1α may reduce tumor growth, there are some limitations to control tumor growth completely. For a more effective therapy for HCC, we investigated HIF-1α independent pathway related tumor growth with angiogenesis. METHODS: We cultured HepG2 cells (HCC cell line) in both normoxia and hypoxia conditions. These cells were divided into three groups: a echinomycin treated group, a echinomycin and quinazoline treated group and a control group without any treatments. Growth morphologies of cells were observed with a microscope after 24 hours. Immunocytochemistry assay was done to detect the angiogenesis during inhibition of HIF-1α and/or NF-κB in hypoxia condition, and compared with results in normoxia condition. RESULTS: In normoxia, the expression of HIF-1α on tumor growth was not found. In hypoxia, inhibition of HIF-1α reduced the tumor growth compared to the control group. But, inhibition of both HIF-1α and NF-κB did not show apparent reduction of tumor growth as shown in HIF-1α only group. CONCLUSIONS: Signaling pathways related to cancer cell growth exist through a vast network. Inhibition of one target molecule may result in over-expression of other molecules related to the tumor growth. For an effective therapy in blocking of the tumor growth, more comprehensive understanding of the network related to signaling pathways on tumor growth is necessary.

Anti-cancer Activity of Osmanthus matsumuranus Extract by Inducing G2/M Arrest and Apoptosis in Human Hepatocellular Carcinoma Hep G2 Cells

BACKGROUND: Osmanthus matsumuranus, a species of Oleaceae, is found in East Asia and Southeast Asia. The bioactivities of O. matsumuranus have not yet been fully understood. Here, we studied on the molecular mechanisms underlying anti-cancer effect of ethanol extract of O. matsumuranus (EEOM). METHODS: Inhibitory effect of EEOM on cell growth and proliferation was determined by WST assay in various cancer cells. To investigate the mechanisms of EEOM-mediated cytotoxicity, HepG2 cells were treated with various concentration of EEOM and analyzed the cell cycle arrest and apoptosis induction by flow cytometry, Western blot analysis, 4,6-diamidino-2-phenylindole (DAPI) staining and DNA fragmentation. RESULTS: EEOM showed the cytotoxic activities in a dose-dependent manner in various cancer cell lines but not in normal cells, and HepG2 cells were most susceptible to EEOM-induced cytotoxicity. EEOM induced G2/M arrest in HepG2 cells associated with decreased expression of cyclin-dependent kinase 1 (CDK1), cyclin A and cylcin B, and increased expression of phospho-checkpoint kinase 2, p53 and CDK inhibitor p21. Immunofluorescence staining showed that EEOM-treated HepG2 increased doublet nuclei and condensed actin, resulting in cell rounding. Furthermore, EEOM-mediated apoptosis was determined by Annexin V staining, chromatin condensation and DNA fragmentation. EEOM caused upregulation of FAS and Bax, activation of caspase-3, -8, -9, and fragmentation of poly ADP ribose polymerase. CONCLUSIONS: These results suggest that EEOM efficiently inhibits proliferation of HepG2 cells by inducing both G2/M arrest and apoptosis via intrinsic and extrinsic pathways, and EEOM may be used as a cancer chemopreventive agent in the food or nutraceutical industry.

Combination of wogonin with 5-fluorouracil exhibits antagonistic effect on human Hep-G2 hepatocellular carcinoma cells / 药学实践杂志

Objective To investigate the antagonistic effect of wogonin in combination with 5-fluorouracil (5-FU) on the proliferation of human Hep-G2 hepatocellular carcinoma cells .Methods Human hepatocellular Hep-G2 cells were divided into experimental group (wogonin group ,5-FU group ,wogonin + 5-FU group) and control group .MTT method was used to eval-uate tumor cell proliferation in vitro ,flow cytometry analysis was used to evaluate tumor cell apoptosis .Results The results showed that the wogonin inhibited the proliferation of tumor cells at the concentrations of 5 ,10 ,20 and 40 μmol/L after 24 h and 48 h treatment respectively (P<0.05);5-FU also inhibited the proliferation of tumor cells at the concentrations of 5 ,10 , 20 and 40 mg/L after 24 h and 48 h treatment respectively (P< 0.05) .However when wogonin was combined with 5-FU (wogonin+5-FU group) ,an antagonistic effect was observed on tumor cell proliferation (P<0.05) .When cells were treated by wogonin+5-FU for 48 h ,the combined index (CI) value slowed a dose-dependent antagonistic effect (P<0.05) .Conclusion Wogonin has anti-tumor effect .However when wogonin was combined with 5-FU ,an obvious antagonistic effect on 5-FU′s anti-tumor action was observed .The underlying mechanism deserves further study .

Short-term Treatment of Daumone Improves Hepatic Inflammation in Aged Mice

Chronic inflammation has been proposed as one of the main molecular mechanisms of aging and age-related diseases. Although evidence in humans is limited, short-term calorie restriction (CR) has been shown to have anti-inflammatory effects in aged experimental animals. We reported on the long-term treatment of daumone, a synthetic pheromone secreted by Caenorhabditis elegans in an energy deficient environment, extends the life-span and attenuates liver injury in aged mice. The present study examined whether late onset short-term treatment of daumone exerts anti-inflammatory effects in the livers of aged mice. Daumone was administered orally at doses of 2 or 20 mg/kg/day for 5 weeks to 24-month-old male C57BL/6J mice. Increased liver macrophage infiltration and gene expression of proinflammatory cytokines in aged mice were significantly attenuated by daumone treatment, suggesting that short-term oral administration of daumone may have hepatoprotective effects. Daumone also dose-dependently suppressed tumor necrosis factor-alpha (TNF-alpha)-induced nuclear factor-kappaB (NF-kappaB) phosphorylation in HepG2 cells. The present data demonstrated that short-term treatment of daumone has anti-inflammatory effects in aged mouse livers possibly through suppression of NF-kappaB signaling and suggest that daumone may become a lead compound targeting aging and age-associated diseases.

Screening of potential active anti-cancer components of Brucea javanica by SMMC-7721 and Hep-G2 comprehensive two dimensional CMC-monolith chro-matography / 药学实践杂志

Objective To screen potential active anti-cancer components of Brucea javanica.Methods This research has em-ployed comprehensive two dimensional chromatographic technology and cell membrane chromatographic technology simultaneously with mass spectrometry as detector .Results Adenosine and Bruceine B were found to be potentially anti-cancer active .Conclusion This study has combined the advantages of online , high speed and high throughput for the screen of potential active components of traditional Chinese medicine .

In vitro and In vivo Effects of the Leaf Extracts of Cassia tora and Cassia sophera in Reducing the Cytotoxicity and Angiogenesis.

Aim: Consumption of C. tora and C. sophera of family caesalpinaceae as leafy vegetables by local folklore has initiated this study to investigate the cytotoxic effect and antiangiogenic effect of their leaf extracts on human cancer cell lines and chick embryo respectively. Study Design: For in vitro studies colon and hepatocarcinoma cell lines were used. For in vivo studies chicken egg chorioallantoic membrane (CAM) assay is used. Methodology: Methanol, ethyl acetate and petroleum ether extracts of leaves were tested for antiproliferative activity using MTT assay, on HCT15 and Hep G2 cell lines. In vivo CAM model was used to study anti-angiogenesis activity of extracts using filter paper discs. Results: All extracts of both plants were toxic to tested cell lines with increasing concentrations and time. Ethyl extract of Cassia tora was found to be most toxic on Hep G2 cell line, though ethyl extract and methanol extracts of both plants were found to give strong antiproliferative activity. Hep G2 was found to be most sensitive to all extracts than HCT15 as inhibited by low IC50 values. Ethyl acetate extracts of both plants exhibited greater anti-angiogenesis activity than other extracts.

Actividad antiproliferativa y anticolesterogénica de estatinas y monoterpenos / Antiproliferative and anticholesterogenic activityof statins and monoterpenes / Atividade antiproliferativa e anticolesterogênicade estatinas e monoterpenos

Las estatinas son inhibidores competitivos de la 3-hidroxi-3-metilglutaril-coenzima A (HMG-CoA) reductasa ampliamente usados en los tratamientos contra las hipercolesterolemias. Los monoterpenos son componentes no nutritivos de la dieta presentes en aceites esenciales de varias plantas que han demostrado tener múltiples efectos en la vía del mevalonato. Se estudia el efecto y mecanismo de acción de monoterpenos presentes en aceites esenciales, así como la combinación de éstos entre sí y con simvastatina sobre la síntesis de colesterol, el metabolismo lipídico y la proliferación celular in vitro en células hepáticas Hep G2 y no hepáticas A549, e in vivo en ratones atímicos huéspedes y no huéspedes de tumores derivado de células A549 implantados en ellos. Se abre así una gran expectativa sobre la potencialidad de la administración conjunta de distintos monoterpenos y de extractos naturales de aceites esenciales en el mejoramiento de las terapias antihipercolesterolemiantes y/o el tratamiento del cáncer, como así también en el potencial sinergismo con estatinas como una alternativa para disminuir las dosis efectivas y los efectos indeseados y/o tóxicos.

Statins are competitive inhibitors of HMG-CoA reductase used in hypercholesterolemic patients. Monoterpenes are non-nutritive dietary components found in the essential oils of many plants with pharmacologic effects on mevalonate metabolism. The study is centered on the effects and action mechanisms of the monoterpene components of essential oils and the combination of monoterpenes between them and combined with simvastatin on cholesterogenesis, lipid metabolism and cellular proliferation in vitro using two established cell lines, Hep G2 (derived from a human hepatoblastoma), A549 (derived from a human lung adenocarcinoma) and in vivo in no host and host nude mice carrying implanted tumors derived from A549. This opens up great expectations about the potential of co-administration of different natural isoprenoids and essential oils in improving anti-cholesterolemic therapies and/or cancer treatment as well as in the potential synergism with statins as an alternative to lower effective doses, decreasing the likelihood of undesired and/or toxic effects.

As estatinas são inibidores competitivos da 3-hidroxi-3-metilglutaril - coenzima A (HMG-CoA) reductase amplamente utilizados nos tratamentos contra as hipercolesterolemias. Os monoterpenos são componentes não nutritivos da dieta encontrados em óleos essenciais de várias plantas que demonstraram ter múltiplos efeitos na via do mevalonato. Estudamos o efeito e o mecanismo de ação de monoterpenos encontrados em óleos essenciais, bem como a combinação deles entre si e com sinvastatina sobre a síntese de colesterol, o metabolismo lipídico e a proliferação celular in vitro em células hepáticas Hep G2 e não hepáticas A549 e in vivo em camundongos atímicos hospedeiros ou não hospedeiros de tumores derivados de células A549 implantadas neles. Isto abre grandes expectativas sobre o potencial da co-administração de diferentes monoterpenos e de extratos naturais de óleos essenciais na melhoria das terapias anti-hipercolesterolemiantes e/ou tratamento do câncer, assim como no potencial sinergismo com estatinas como uma alternativa para reduzir as doses efetivas e os efeitos indesejáveis e/ou tóxicos.

Synthesis, Molecular docking and Biological evaluation of 4-Cycloalkylidineamino 1, 2-Naphthoquinone Semicarbazones as Anticancer agents

Objective: In an effort to etablish new candidates with improved antineoplastic activity, 4-cycloalkylidineamino 1,2-naphthoquinone semicarbazones were synthesized, characterized and evaluated for anticancer activity. Method: The desired compounds were synthesized by condensation of 4- amino1, 2-naphthoquinone with cyclic ketones and further subsequent reaction of this product with semicarbazide hydrochloride. Compounds were characterized by FT-IR, 1H NMR, 13C NMR, elemental analysis and screened for antiproliferative activity against three human cancer cell lines (HepG2, MG-63 and MCF-7) by MTT assay using doxorubicin as standard. Docking was performed by using the Glide 5.7 integrated with Maestro 9.2 (Schr?dinger, LLC, 2011) to understand the binding preference of synthesized compounds with target enzyme topoisomerase-II. Results: 4-(cyclohexylideneamino) [1, 2] naphthoquinone 2-semicarbazone was found to be most active cytotoxic agent against all cancer cell lines with IC50 values in the range of 5.58–6.31 μM. Results of molecular docking were also well correlated in vitro cytotoxicity assay. Insilico ADME studies revealed the drug likeliness of compounds. Conclusions: The synthesized compounds were found to have significant anticancer activity and able to enter in higher phases of the drug development process due to favorable pharmacokinetic properties.

Effects of NS-398 on the proliferation and apoptosis of HepG2 cells / 中国病理生理杂志

AIM: To evaluate the effects of NS-398, a cyclooxygenase-2(COX-2) inhibitor, on the proliferation and apoptosis in HepG2 cells. METHODS: The effects of NS-398 on the proliferation of HepG2 cells was evaluated by MTT. DNA fragmentation gel analysis was used to analyze the apoptotic cells; DNA ploidy and apoptotic cell percentage were examined by flow cytometry. Furthermore, the expression of COX-2 and Bcl-2 mRNA was identified by competitive RT-PCR. RESULTS: NS-398 inhibited cell proliferation and induced apoptosis in HepG2 in a concentration-dependent manner. DNA ploidy analysis showed that S phase cells were significantly decreased with NS-398 concentration increasing. The quiescent G_0/G_1 phase was accumulated with decreasing of Bcl-2 mRNA. Whereas NS-398 had no effect on the expression of COX-2 mRNA, no correlations were found between COX-2 mRNA and the HepG2 cell proliferation and apoptosis induced by NS-398 (r=0.056 and r=0.119, respectively). CONCLUSION: NS-398 significantly inhibits the proliferation and induces apoptosis in HepG2. Mechanisms may be involved in accumulation of quiescent G_0/G_1 phase and decrease in Bcl-2 mRNA expression, but independent to COX-2 mRNA expression. [

Use Of Metabolically Competent Human Hepatoma Cells of The Detection Of Mutagens And Antimutagens.

The human hepatoma cell line (Hep G2) has retained the activities of various phase I and phase II enzymes which play a crucial role in the activation/detoxification of genotoxic procarcinogens and reflects the metabolism of such compounds in vivo better than experimental models with metabolically incompetent cells and exogenous activation mixtures. In recent years, methodologies have been developed which enable the detection of genotoxic effects in Hep G2 cells. Appropriate endpoints are the induction of 6-TGr mutants, of micronuclei and of comets (single cell electrophoresis assays). It has been demonstrated that various classes of environmental carcinogens, such as nitrosamines, aflatoxins, aromatic and heterocyclic amines and polycyclic aromatic hydrocarbons can be detected in genotoxicity assays with Hep G2 cells. Furthermore, it has been shown that these assays can distinguish between structurally related carcinogens and non-carcinogens, and positive results have been obtained with rodent carcinogens (such as safrol and hexamethylphosphoramide) which give false negative results in conventional in vitro assays with rat liver homogenates. Hep G2 cells have also been used in antimutagenicity studies and can identify mechanisms not detected in conventional in vitro systems such as induction of detoxifying enzymes, inactivation of endogenously formed DNA- reactive metabolites and intracellular inhibition of activating enzymes.

Inhibition of tetramethylpyrazine-containing serum on proliferation of human liver cancer cells Hep G_2 / 中草药

Objective To observe the effects of rat tetramethylpyrazine (TMP)-containing serum on the proliferation of human liver cancer cells Hep G2. Methods Thirty SD male rats were divided into three groups randomly and the serum was collected after ip TMP with the dosage of 143.0, 71.5 mg/kg or NS 0.8 mL to prepare the TMP-containing serum in large- and small-dose groups and NS group as well. A reversed-phase high performance liquid chromatography (RP-HPLC) method was used to determine the TMP concentration in rat serum. Human liver cancer cells Hep G2 was treated with rat TMP-containing serum for 48 h. Inhibition of the TMP-containing serum on proliferation of Hep G2 was detected by MTT assay. Results The serum of large dose TMP (20%, 10%, and 5%) and small dose TMP (20% and 10%) could obviously inhibit Hep G2 multiplication (P

The effect of STAT3 decoy ODNs on the growth and apoptosis of Hep G2 cells / 临床检验杂志

Objective To investigate the effect of STAT3 decoy ODNs on the growth and apoptosis of hepatoma cells Hep G2 and the related mechanism.Methods STAT3 decoy ODNs,synthesized in vitro,was transferred into Hep G2 cells by cationic lipid.The cell growth curve was used to reflect the growth and proliferation capacity of Hep G2,and annexin-V/PI staining method was used to calculate apoptic cells by FCM.Real time-PCR was used to quantitatively detect the expression of bcl-xL,cyclin D1,and c-myc mRNA in Hep G2.Results FCM assay and fluorescence microscopy demonstrated that STAT3 decoy ODNs was successfully transferred into Hep G2 cells(90.2%).Decoy ODNs inhibted the growth of Hep G2 cells.After treated with decoy ODNs 48 h,the percentage of early apoptotic cells was(22.86 ? 2.63)% and that of late apoptotic cells was(23.00 ? 2.76)%.Real time-PCR indicated that Hep G2 cells transfected with STAT3 decoy ODNs had decreased the mRNA expression of bcl-xL,cyclin D1 and c-myc.Conclusions STAT3 decoy ODNs inhibited the growth of Hep G2 cells and induce the apoptosis.The mechanism may be associated with decreased expression of bcl-xL,cyclin D1 and c-myc mRNA.