scholarly journals Evaluation of anti-proliferative activity of simvastatin and atorvastatin on MCF7 cell line compared with doxorubicin using MTT test

Statins are effective to lower the cholesterol level and protect against cardiovascular disease. Recent studies showed that statins have pleiotropic effect and can be used to treat many types of diseases like neurodegenerative disorders, stroke, and cancer. Statins inhibit cell proliferation by suppression of mevalonate pathway leading to desregu-lation of cell signal transduction of some membrane receptor protein which is important for gene transcription. This study was done to evaluate the anti-proliferative activity of simvastatin and atorvastatin on MCF7 cell line alone and in combination with anathracycline chemotherapy drug (doxo-rubicin) using MTT assay. The results showed that simvastatin and atorvastatin had significant anti-proliferative effect on MCF7 cell line in dose-dependent manner with an IC50 10.10 μM and 12.3 μM respect-tively. Moreover, the combination of atorvastatin and simvastatin with (1 μM) doxorubicin had higher cytotoxic effect with an IC50 = 0.07 μM and 0.05μM respectively than doxoru-bicin alone IC50 = 1.9 μM. In conclusion, simvastatin and atorvastatin had anti-proliferative effect on MCF7 cell line and displayed significant synergism with doxorubicin which will help in enhancing efficacy of doxorubicin and decrease the adverse effect.

2016 ◽  
Vol 6 (9) ◽  
pp. 587 ◽  
Author(s):  
Roula  Abdel-Massih ◽  
Venicia Hawach ◽  
Marie-Anne Boujaoude

Background: Pectin is a heterogeneous polysaccharide mainly present in citrus fruits and has different biological activities.Objective: High molecular weight Citrus Pectin and modified citrus pectin (MCP) were tested for their cytotoxic, anti-proliferative, and anti-oxidant activity.Methods: The cytotoxicity of pectin was studied against HaCaT cell line (human keratinocyte cell line) using Trypan blue method and LDH-cytotoxicity assay. Anti-proliferative activity was assayed using a WST-1 proliferation kit. Antioxidant activity was determined using the DPPH scavenging assay.Results: MCP and Pectin both reduced the viability of HaCaT cells in a dose dependent manner; however MCP was found to be more cytotoxic than high molecular weight citrus pectin since it had a lower IC50 (300ug/ul). At non-cytotoxic concentrations, the viability of cells decreased with increase of concentration of MCP as determined by the WST-1. MCP exhibited a higher antioxidant effect than pectin (SC50 at a concentration range between 2 and 4mg/ml).Conclusion: This study suggests that MCP exhibits a stronger cytotoxic and anti-proliferative effect on HaCaT cell line than pectin. The most probable explanation of this observation is the different effect due to the variable molecular weight and exposed side-chains of MCP and high molecular weight citrus pectin. Keywords: Cytotoxic, Anti-proliferative, Pectin, MCP, HaCaT cell line 


Contrast- induced nephropathy (CIN) is an elevation of serum creatinine of ≥ 0.5 mg/dL from baseline after two to three days of exposure to contrast substance if there is no other cause for acute kidney injury. Atorvastatin may protect normal kidney physiology from contrast- induced kidney injury by effects unrelated to hypolipidemia termed pleiotropic effect by decline of endothelin production, angiotensin system down regulation, and under expression of endothelial adhesion molecules. This study was conducted to assess the strategy by which atorvastatin can achieve protective effect for kidneys after exposure to contrast media in an animal model. A 40 male rats were distributed randomly into 4 groups; ten rats for each: group (1): given normal saline; group (2): CIN group given iopromide as contrast media; group (3): given atorvastatin (20mg/kg) and iopromide; and group (4): given atorvastatin (40mg/kg) and iopromide. Blood collected by cardiac puncture for detection of serum glutathione, malondialdehyde, matrix metalloproteinase-9, and interleukin-18. The results have shown a significant increase in inflammatory and oxidative stress markers in contrast media group, and significant reduction in these markers in atorvastatin treated groups, in a dose-dependent manner. As conclusion, atorvastatin mechanism for protection against CIN in a dose-dependent manner can mediate by anti-inflammatory and antioxidant effects.


2014 ◽  
Vol 25 (3-4) ◽  
pp. 24-33
Author(s):  
O. I. Dzjuba ◽  
M. V. Yatsenko

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.


1997 ◽  
Vol 273 (5) ◽  
pp. E880-E890 ◽  
Author(s):  
Wenhan Chang ◽  
Tsui-Hua Chen ◽  
Stacy A. Pratt ◽  
Benedict Yen ◽  
Michael Fu ◽  
...  

Parathyroid cells express Ca2+-conducting cation currents, which are activated by raising the extracellular Ca2+ concentration ([Ca2+]o) and blocked by dihydropyridines. We found that acetylcholine (ACh) inhibited these currents in a reversible, dose-dependent manner (50% inhibitory concentration ≈10−8 M). The inhibitory effects could be mimicked by the agonist (+)-muscarine. The effects of ACh were blunted by the antagonist atropine and reversed by removing ATP from the pipette solution. (+)-Muscarine enhanced the adenosine 3′,5′-cyclic monophosphate (cAMP) production by 30% but had no effect on inositol phosphate accumulation in parathyroid cells. Oligonucleotide primers, based on sequences of known muscarinic receptors (M1-M5), were used in reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify receptor cDNA from parathyroid poly (A)+ RNA. RT-PCR products displayed >90% nucleotide sequence identity to human M2- and M4-receptor cDNAs. Expression of M2-receptor protein was further confirmed by immunoblotting and immunocytochemistry. Thus parathyroid cells express muscarinic receptors of M2 and possibly M4 subtypes. These receptors may couple to dihydropyridine-sensitive, cation-selective currents through the activation of adenylate cyclase and ATP-dependent pathways in these cells.


2021 ◽  
Vol 36 (1) ◽  
pp. 1029-1047
Author(s):  
Myriam González ◽  
María Ovejero-Sánchez ◽  
Alba Vicente-Blázquez ◽  
Manuel Medarde ◽  
Rogelio González-Sarmiento ◽  
...  

1989 ◽  
Vol 257 (5) ◽  
pp. C888-C895 ◽  
Author(s):  
E. Coezy ◽  
I. Darby ◽  
J. Mizrahi ◽  
B. Cantau ◽  
M. H. Donnadieu ◽  
...  

The aim of this study was to examine in Hep G2, a human hepatoma-derived cell line, the presence of angiotensin II (ANG II) receptors and the effect of ANG II and its analogues on angiotensinogen production. The presence of ANG II receptors was demonstrated using a long-acting ANG II analogue, 125I-labeled [Sar1]ANG II. A single class of specific binding sites was identified in these cells with a dissociation constant (Kd) of 2 nM. The number and affinity of these binding sites were not changed by [Sar1]ANG II treatment over 24 h. ANG II showed an inhibitory effect on angiotensinogen production. [Sar1]ANG II also exhibited a similar inhibitory effect as that of ANG II but to a greater extent and therefore was used throughout these studies. [Sar1]ANG II inhibited angiotensinogen production in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) of 2 nM. Other ANG II analogues showed similar effects on angiotensinogen production. In order of decreasing ability, they were [Sar1]ANG II greater than [Sar1-Ala8]ANG II greater than [Sar1-Val8]ANG II greater than [Sar1-Val5-(Br5)-Phe8]ANG II greater than [Sar1-Val5-DPhe8]ANG II. Results of these studies show that the Hep G2 cell possesses specific ANG II receptors and that [Sar1]ANG II induces a dose-dependent inhibition of angiotensinogen production in this system.


Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 444 ◽  
Author(s):  
Sangiliyandi Gurunathan ◽  
Muniyandi Jeyaraj ◽  
Min-Hee Kang ◽  
Jin-Hoi Kim

Generally, platinum nanoparticles (PtNPs) are considered non-toxic; however, toxicity depends on the size, dose, and physico-chemical properties of materials. Owing to unique physico-chemical properties, PtNPs have emerged as a material of interest for several biomedical applications, particularly therapeutics. The adverse effect of PtNPs on the human monocytic cell line (THP-1) is not well-established and remains elusive. Exposure to PtNPs may trigger oxidative stress and eventually lead to inflammation. To further understand the toxicological properties of PtNPs, we studied the effect of biologically synthesized ultra-small PtNPs on cytotoxicity, genotoxicity, and proinflammatory responses in the human monocytic cell line (THP-1). Our observations clearly indicated that PtNPs induce cytotoxicity in a dose-dependent manner by reducing cell viability and proliferation. The cytotoxicity of THP-1 cells correlated with an increase in the leakage of lactate dehydrogenase, generation of reactive oxygen species, and production of malondialdehyde, nitric oxide, and carbonylated proteins. The involvement of mitochondria in cytotoxicity and genotoxicity was confirmed by loss of mitochondrial membrane potential, lower ATP level, and upregulation of proapoptotic and downregulation of antiapoptotic genes. Decreases in the levels of antioxidants such as reduced glutathione (GSH), oxidized glutathione (GSH: GSSG), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and thioredoxin (TRX) were indicative of oxidative stress. Apoptosis was confirmed with the significant upregulation of key apoptosis-regulating genes. Oxidative DNA damage was confirmed by the increase in the levels of 8-oxodG and 8-oxoG and upregulation of DNA damage and repair genes. Finally, the proinflammatory responses to PtNPs was determined by assessing the levels of multiple cytokines such as interleukin-1β (IL-1β), IL-6, IL-8, tumor necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), and monocyte chemoattractant protein 1 (MCP-1). All the cytokines were significantly upregulated in a dose-dependent manner. Collectively, these observations suggest that THP-1 cells were vulnerable to biologically synthesized ultra-small PtNPs.


1996 ◽  
Vol 313 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Geneviève VALLETTE ◽  
Anne JARRY ◽  
Jean-Eric BRANKA ◽  
Christian L. LABOISSE

We evaluated the effects of two NO donors, sodium nitroprusside (SNP) and 3-morpholino-sydnonimine (SIN-1), characterized by alternative redox states, i.e. nitrosonium ion (NO+) and nitric oxide (NO•) respectively, on intracellular interleukin-1 (IL-1) production, by a human colonic epithelial cell line (HT29-Cl.16E). SNP was able to induce intracellular IL-1α production up to 10 h incubation, in a dose-dependent manner. Several experiments provide evidence that the NO+ redox form, and not the free radical NO•, is implicated in the IL-1α production: (i) SIN-1, devoid of any NO+ character, led to a very weak IL-1 production as compared with SNP; (ii) the reductive action of a thiol such as cysteine on NO+ led to a dose-dependent increase in NO• concentration, measured as NO2-/NO3- accumulation, and to a large decrease in IL-1 production. Dibutyryl cGMP had no effect on IL-1 production, this finding supporting the concept that a cGMP-independent pathway is involved in the intracellular signalling of NO+. Together these results point out that NO, depending on its redox form, is able to modulate IL-1 production in cultured colonic epithelial cells.


2019 ◽  
Vol 17 (1) ◽  
pp. 943-954
Author(s):  
Abeer N. Al-romaizan ◽  
Thoraya S. Jaber ◽  
Nesreen S. Ahmed

AbstractA series of new 2-phenyl-7-methyl-1,8-naphthyridine derivatives with variable substituents at C3 were synthesized for an in vitro evaluation of their anticancer activity against human breast cancer cell line (MCF7). On one hand, compounds 3f, 6f, 8c, and 10b showed IC50 values (6.53, 7.88, 7.89, 7.79 μM, respectively) compared to that of the mentioned drug staurosparine (IC50 = 4.51 μM). On the other hand, derivatives 10c, 8d, 4d, 10f and 8b displayed better activity than staurosporin with IC50 values (1.47, 1.62, 1.68, 2.30, 3.19 μM, respectively).


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