scholarly journals Targeting study of HepG2 hepatoma cells in vitro by drug-loaded pectin-based nanoparticles

2019 ◽  
Author(s):  
Anil Shumroni ◽  
David Gupta
Keyword(s):  
Mtt Assay ◽  
Hepg2 Cells ◽  
Hepatoma Cell ◽  
Drug Loading ◽  
A549 Cells ◽  
Cell Uptake ◽  
Dependent Manner ◽  
Human Hepatoma Cell ◽  
Significant Difference ◽  
Dose Dependent

AbstractThe biodegradable and biodegradable natural polysaccharide has always been used as a drug delivery system, and has the following advantages: It can prolong the biological half life of the drug and reduce the side effects of the drug. This experiment aimed to prepare a 5-fluorouracil (5-FU) nanoparticle (P-5-FU) drug-loading system based on pectin, and explored a large number of pectin-based nano drug-loading systems. The galactose residue is a natural target that targets human hepatoma cell HepG2. MTT assay was used to determine the proliferation inhibition effect of drug-loaded pectin-based nanoparticles on HepG2 and A549 cells. MTT assay showed that P-5-FU inhibited the proliferation of HepG2 cells in a dose-dependent manner, and the effect was stronger than 5-FU. P-5-FU also inhibited the proliferation of A549 cells in a dose-dependent manner, but there was no significant difference compared with 5-FU. High performance liquid chromatography (HPLC) on two kinds of cells loaded with drug-loaded nanoparticles the uptake and targeting were measured. The results of cell uptake showed that the uptake of P-5-FU by HepG2 cells was significantly higher than that of 5-FU, but there was no significant difference in the uptake of P-5-FU and 5-FU by A549 cells. There was no significant difference in the uptake of P-5-FU and 5-FU between the two cells after the galactose-saturated ASGPR binding site. The results indicate that pectin-based nano drug-loaded particles can specifically target highly expressed cells.

Growth Inhibition and Cell Cycle Arrest of Kappa-Selenocarrageenan and Paclitaxel on HepG2 Cells

2011 ◽  
Vol 343-344 ◽  
pp. 530-534 ◽  
Author(s):  
Na Ling
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Western Blotting ◽  
Hepg2 Cells ◽  
Hepatoma Cell ◽  
Cyclin A ◽  
S Phase ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Human Hepatoma Cell

To evaluate the anti-proliferative effect of kappa-selenocarrageenan (KSC) in combination with paclitaxel (Taxol) on human hepatoma cell line HepG2 and their synergistic effect. The cytotoxic effect of drugs on HepG2 cells was measured by MTT assay, and the King’s principle was used to evaluate the interaction of drug combination. Cell cycle and apoptotic rate were detected by flow cytometry (FCM). Expression of cyclin A, chk2, Cdc25A and cdk2 were detected by flow cytometry and western blotting. KSC and Taxol demonstrated growth inhibitory effect on HepG2 cells in a dose-dependent manner, with the IC50 values of Taxol decreased dramatically from 1.684 nmol/L to 0.272 nmol/L while combining with 30 mg/L KSC (P<0.01). In addition, additive activity was observed when 30 mg/L KSC was combined with Taxol (0.5~5 nmol/L) (q=0.85~1.15). FCM results showed that KSC and Taxol both blocked cell cycle in S phase and their combination enhanced S phase arrest. Western blotting analysis revealed that Cyclin A and chk2 protein expression in HepG2 cells increased but Cdc25A and cdk2 expression decreased.

Ecological and physiological as well as biochemical properties of representatives of the Genus sedum L.

2014 ◽  
Vol 25 (3-4) ◽  
pp. 24-33
Author(s):  
O. I. Dzjuba ◽  
M. V. Yatsenko
Keyword(s):  
Nitric Oxide ◽  
Cell Line ◽  
Methanol Extract ◽  
Hepatoma Cell ◽  
Ethanol Extract ◽  
Biochemical Properties ◽  
Biologically Active ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Dose Dependent

The article deals with the history of the study and the current state of research of physiological and biochemical properties of the plant genus Sedum that are useful for human and has been used in folk medicine for many years. It was noticed that antioxidant properties of extracts from plants S. sarmentosum, S. sempervivoides, S. takesimense were caused by the presence of phenolic compounds. Methanol extract of plants S. takesimense exhibited strong scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals as well as significant inhibitory effects on lipid peroxidation and low density lipoprotein (LDL) oxidation induced by a metal ion Cu2+. Various immunomodulatory activities of various fractions of plants extracts (S. dendroideum, S. kamtschaticum, S. sarmentosum, S. telephium) are observed. It was shown that the ethanol extract of S. sarmentosum and it’s fractions suppressed specific antibody and cellular responses to ovalbumin in mice. The methanol extract of plants S. sarmentosum reduced the levels of anti-inflammatory markers, such as volume of exudates, number of polymorphonuclear leukocytes, suppressed nitric oxide synthesis in activated macrophages via suppressed induction of inducible nitric oxide synthase (iNOS). Polysaccharides fractions from plants S. telephium inducing productions of tumor necrosis factor alpha (TNF-α), increasing the intensity of phagocytosis in vitro and in vivo. Methanol extract from the whole part of S. kamtschaticum strongly inhibit PGE2 production from lipopolysaccharide-induced RAW 264.7 cells, a mouse macrophage cell line via modulating activity in gene expression of the enzyme cyclooxygenase-2 (COX-2). The methanol extract of plants S. sarmentosum and the major kaempferol glycosides from S. dendroideum have antinociceptive activity. It was noticed that anti-adipogenic activity of extracts from plants S. kamtschaticum were caused by inhibition of peroxisome-proliferator-activated receptor γ (PPARγ) expression and it’s dependent target genes, such as genes encoding adipocyte protein 2 (аР2), lipoprotein lipase (LPL), adiponectin and CD36. Polysaccharides fractions from S. telephium cause inhibition of cell adhesion of human fibroblast (MRC5) to laminin and fibronectin via interfere with integrin-mediated cell behaviour and they contributed to the role of polysaccharides in cell-matrix interaction. The methanol extract of plants S. sarmentosum exhibited a significant inhibitory activity in the chick embryo chorioallantoic membrane angiogenesis in a dose-dependent manner. The crude alkaloid fraction of S. sarmentosum caused a dose-dependent inhibition of cell proliferation on murine hepatoma cell line BNL CL.2 and human hepatoma cell line HepG2 without necrosis or apoptosis. Alkaloids from plants S. sarmentosum may improve survival of hepatoma patients via the inhibition of excessive growth of tumor cells. Plant’s juices have antiviral activity (S. sarmentosum, S. spurium, S. stahlii). Crude ethanol extract S. praealtum have spermicidal activity of the in mice and a relevant inhibitory effect of aqueous extract on human spermatozoa motility as well as an anti-fertilizing activity in rats. Hepatoprotective triterpenes, e.g., δ-amyrone, 3-epi-δ-amyrin, δ-amyrin and sarmentolin were isolated from S. sarmentosum. 2- and 2,6-substituted piperidine alkaloids (e.g., norsedamine, allosedridine, sedamine, allosedamine) are observed in plants S. acre, which in the presence of data on the use of pyridine and piperidine derivatives for treating neurodegenerative diseases (e.g., Alzheimer's disease), points on the promising research in this area. Taking into account that biologically active compounds are accumulated in the aboveground vegetative organs of plants of Sedum, the prospects of further study of the use of Sedum for the purposes of biotechnology and in the pharmaceutical industry becomes apparent. This work extends the existing views regarding the use of plants Sedum.

scholarly journals The Modulation of PCSK9 and LDLR by Supercritical CO2 Extracts of Mentha longifolia and Isolated Piperitone Oxide, an In Vitro Study

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3886
Author(s):  
Stefania Sut ◽  
Irene Ferrarese ◽  
Maria Giovanna Lupo ◽  
Nicola De Zordi ◽  
Elisa Tripicchio ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
Density Lipoprotein ◽  
In Vitro Study ◽  
Volatile Constituent ◽  
Dependent Manner ◽  
Human Hepatoma Cell ◽  
Concentration Dependent Manner

In the present study the ability of supercritical carbon dioxide (SCO2) extracts of M. longifolia L. leaves to modulate low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression was evaluated in cultured human hepatoma cell lines Huh7 and HepG2. Two SCO2 extracts, one oil (ML-SCO2) and a semisolid (MW-SCO2), were subjected to detailed chemical characterization by mono- and bidimensional nuclear magnetic resonance (1D, 2D-NMR), gas chromatography coupled with mass spectrometry (GC-MS) and liquid chromatography coupled with mass spectrometry (LC-MS). Chemical analysis revealed significant amounts of fatty acids, phytosterols and terpenoids. ML-SCO2 was able to induce LDLR expression at a dose of 60 µg/mL in HuH7 and HepG2 cell lines. Furthermore, ML-SCO2 reduced PCSK9 secretion in a concentration-dependent manner in both cell lines. Piperitone oxide, the most abundant compound of the volatile constituent of ML-SCO2 (27% w/w), was isolated and tested for the same targets, showing a very effective reduction of PCSK9 expression. The overall results revealed the opportunity to obtain a new nutraceutical ingredient with a high amount of phytosterols and terpenoids using the SCO2 extraction of M. longifolia L., a very well-known botanical species used as food. Furthermore, for the first time we report the high activity of piperitone oxide in the reduction of PCSK9 expression.

scholarly journals Pyrrolizidine Alkaloids Induce Cell Death in Human HepaRG Cells in a Structure-Dependent Manner

2020 ◽  
Vol 22 (1) ◽  
pp. 202
Author(s):  
Josephin Glück ◽  
Julia Waizenegger ◽  
Albert Braeuning ◽  
Stefanie Hessel-Pras
Keyword(s):  
Cell Death ◽  
Cell Viability ◽  
Pyrrolizidine Alkaloids ◽  
Defense Mechanism ◽  
Hepatoma Cell ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Human Hepatoma Cell

Pyrrolizidine alkaloids (PAs) are a group of secondary metabolites produced in various plant species as a defense mechanism against herbivores. PAs consist of a necine base, which is esterified with one or two necine acids. Humans are exposed to PAs by consumption of contaminated food. PA intoxication in humans causes acute and chronic hepatotoxicity. It is considered that enzymatic PA toxification in hepatocytes is structure-dependent. In this study, we aimed to elucidate the induction of PA-induced cell death associated with apoptosis activation. Therefore, 22 structurally different PAs were analyzed concerning the disturbance of cell viability in the metabolically competent human hepatoma cell line HepaRG. The chosen PAs represent the main necine base structures and the different esterification types. Open-chained and cyclic heliotridine- and retronecine-type diesters induced strong cytotoxic effects, while treatment of HepaRG with monoesters did not affect cell viability. For more detailed investigation of apoptosis induction, comprising caspase activation and gene expression analysis, 14 PA representatives were selected. The proapoptotic effects were in line with the potency observed in cell viability studies. In vitro data point towards a strong structure–activity relationship whose effectiveness needs to be investigated in vivo and can then be the basis for a structure-associated risk assessment.

scholarly journals Targeting BMI-1 with PLGA–PEG nanoparticle-containing PTC209 modulates the behavior of human glioblastoma stem cells and cancer cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Elham Poonaki ◽  
Fatemeh Ariakia ◽  
Mohammad Jalili-Nik ◽  
Mehdi Shafiee Ardestani ◽  
Gholamhossein Tondro ◽  
...  
Keyword(s):  
Drug Loading ◽  
Polycomb Group ◽  
Dependent Manner ◽  
Migration Ability ◽  
Jnk Signaling ◽  
Human Glioblastoma ◽  
Core Member ◽  
Ic50 Values ◽  
Human Gbm ◽  
Dose Dependent

AbstractDespite advances in glioblastoma (GBM) treatments, current approaches have failed to improve the overall survival of patients. The oncogene BMI-1, a core member of the polycomb group proteins, is a potential novel therapeutic target for GBM. To enhance the efficacy and reduce the toxicity, PTC209, a BMI-1 inhibitor, was loaded into a PLGA–PEG nanoparticle conjugated with CD133 antibody (Nano-PTC209) and its effect on the behavior of human GBM stem-like cells (GSCs) and the human glioblastoma cell line (U87MG) was assessed. Nano-PTC209 has a diameter of ~ 75 nm with efficient drug loading and controlled release. The IC50 values of Nano-PTC209 for GSCs and U87MG cells were considerably lower than PTC209. Nano-PTC209 significantly decreased the viability of both GSCs and U87MG cells in a dose-dependent manner and caused a significant enhancement of apoptosis and p53 levels as well as inhibition of AKT and JNK signaling pathways. Furthermore, Nano-PTC209 significantly inhibited the migration ability, decreased the activity of metalloproteinase-2 and -9, and increased the generation of reactive oxygen species in both GSCs and U87MG cells. Our data indicate that PLGA–PEG nanoparticle conjugated with CD133 antibody could be an ideal nanocarrier to deliver PTC209 and effectively target BMI-1 for potential approaches in the treatment of GBM.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

Human MutT Homolog 1 (MTH1) Inhibitor Reduces the Biological Activity of Ovarian Carcinoma Cells

2022 ◽  
Vol 12 (5) ◽  
pp. 907-913
Author(s):  
Liyan Zhong ◽  
Yi Yi ◽  
Qian Liu ◽  
Yan Peng
Keyword(s):  
Biological Activity ◽  
Ovarian Carcinoma ◽  
Biological Activities ◽  
Carcinoma Cells ◽  
Dependent Manner ◽  
Ovarian Carcinoma Cells ◽  
Proliferative Rate ◽  
Skov3 Cells ◽  
Significant Difference ◽  
Dose Dependent

This study intends to discuss the mechanism of MTH1 inhibitor (TH588) in the biological activity of ovarian carcinoma cells. A2780 and SKOV-3 cells were treated with different concentrations of TH588 and assigned into AT group (control), BT group (8 μmol/L TH588), CT group (16 μmol/L), DT group (32 μmol/L), ET group (64 μmol/L) and FT group (128 μmol/L) followed by measuring level of Bcl-2 and Bax by Western blot and PCR, and cell biological activities by MTT, FCM and Transwell chamber assay. The cell proliferative rate was not affected in AT group, but was lower in other groups in a reverse dose-dependent manner. There was significant difference on apoptotic rate and cell invasion among groups with increased apoptosis and reduce invasion after TH588 treatment. FT group showed lowest expression of Bcl-2 and Bax compared to other groups. In conclusion, the biological activity of A2780/SKOV3 cells could be reduced by MTH1 inhibitor which was probably through regulation of Bax and Bcl-2 expression.

Cadmium and platinum suppression of erythropoietin production in cell culture: clinical implications

Blood ◽  
2000 ◽  
Vol 96 (12) ◽  
pp. 3743-3747 ◽  
Author(s):  
Hyogo Horiguchi ◽  
Fujio Kayama ◽  
Etsuko Oguma ◽  
William G. Willmore ◽  
Pavel Hradecky ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Damage ◽  
Hepatoma Cell ◽  
Inhibitory Effect ◽  
Binding Activity ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Toxic Exposure ◽  
Human Hepatoma Cell ◽  
Simultaneous Exposure

Abstract Both toxic exposure to cadmium and cancer therapy with cisplatin (CDDP) can induce anemia in patients owing to the insufficient production of erythropoietin (EPO). Therefore, the effects of cadmium chloride (Cd) and CDDP in the Hep3B human hepatoma cell line, which up-regulates EPO expression in response to hypoxia and cobalt (Co), were investigated. The induction of binding activity of the HIF-1 transcription factor and EPO mRNA expression and protein production were suppressed by Cd and CDDP in a dose-dependent manner with no apparent cell damage. Mercuric chloride also suppressed hypoxia- and Co-induced EPO production, mRNA expression, and HIF-1 binding in a manner similar to Cd and CDDP, whereas zinc chloride suppressed Co-induced EPO production, mRNA expression, and HIF-1 binding but did not affect hypoxia induction or that observed after simultaneous exposure to hypoxia and Co. In contrast, lead and tin salts had no effect on HIF-1 activation or EPO expression. These results indicate that Cd and CDDP have a strong and specific inhibitory effect on hypoxia- and Co-induced signaling and EPO induction in hepatic cells. It is likely that these agents cause anemia by directly impacting EPO production in the kidney.

Comparative cytotoxicity and apoptotic pathways induced by nanosilver in human liver HepG2 and L02 cells

2018 ◽  
Vol 37 (12) ◽  
pp. 1293-1309 ◽  
Author(s):  
Y Xue ◽  
J Wang ◽  
Y Huang ◽  
X Gao ◽  
L Kong ◽  
...  
Keyword(s):  
Cell Line ◽  
Hepg2 Cells ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Hepatoma Cell ◽  
Death Receptor ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Death Receptor Pathway ◽  
L02 Cells

Silver nanoparticles are used in many commercial products in daily life. Exposure to nanosilver has hepatotoxic effects in animals. This study investigated the cytotoxicity associated with polyvinylpyrrolidone-coated nanosilver (23.44 ± 4.92 nm in diameter) exposure in the human hepatoma cell line (HepG2) and normal hepatic cell line (L02), and the molecular mechanisms induced by nanosilver in HepG2 cells. Nanosilver, in doses of 20–160 μg mL−1 for 24 and 48 h, reduced cell viability in a dose- and time-dependent manner and induced cell membrane leakage and mitochondria injury in both cell lines; these effects were more pronounced in HepG2 cells than in L02 cells. Intracellular oxidative stress was documented by reactive oxygen species (ROS) being generated in HepG2 cells but not in L02 cells, an effect possibly due to differential uptake of nanosilver by cancer cells and normal cells. In HepG2 cells, apoptosis was documented by finding that ROS triggered a decrease in mitochondrial membrane potential, an increase in cytochrome c release, activation of caspase 3 and caspase 9, and a decrease in the ratio of Bcl-2/Bax. Furthermore, nanosilver activated the Fas death receptor pathway by downregulation of nuclear factor-κB and activation of caspase 8 and caspase 3. These results suggest that apoptosis induced by nanosilver in HepG2 cells is mediated via a mitochondria-dependent pathway and the Fas death receptor pathway. These findings provide toxicological and mechanistic information that can help in assessing the effects of nanosilver in biological systems, including the potential for anticancer activities.

scholarly journals MK-571, a Cysteinyl Leukotriene Receptor 1 Antagonist, Inhibits Hepatitis C Virus Replication

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Isaac Ruiz ◽  
Quentin Nevers ◽  
Eva Hernández ◽  
Nazim Ahnou ◽  
Rozenn Brillet ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hepatoma Cell ◽  
Hcv Rna ◽  
Dependent Manner ◽  
Cysteinyl Leukotriene ◽  
Leukotriene Receptor ◽  
Cysteinyl Leukotriene Receptor ◽  
Dose Dependent ◽  
Rna Levels

ABSTRACT The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct-acting antiviral (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7.5 cells stably harboring a subgenomic genotype 1b replicon. A dose-dependent decrease of HCV RNA levels was observed upon MK-571 administration, with a 50% effective concentration (EC50 ± standard deviation) of 9 ± 0.3 μM and a maximum HCV RNA level reduction of approximatively 1 log10. MK-571 also reduced the replication of the HCV full-length J6/JFH1 model in a dose-dependent manner. However, probenecid and apigenin homodimer (APN), two specific inhibitors of MRP-1, had no effect on HCV replication. In contrast, the CysLTR1 antagonist SR2640 increased HCV-subgenomic replicon (SGR) RNA levels in a dose-dependent manner, with a maximum increase of 10-fold. In addition, a combination of natural CysLTR1 agonist (LTD4) or antagonists (zafirlukast, cinalukast, and SR2640) with MK-571 completely reversed its antiviral effect, suggesting its anti-HCV activity is related to CysLTR1 rather to MRP-1 inhibition. In conclusion, we showed that MK-571 inhibits HCV replication in hepatoma cell cultures by acting as a CysLTR1 receptor antagonist, thus unraveling a new host-virus interaction in the HCV life cycle.

Sign in / Sign up

Export Citation Format

Share Document