scholarly journals Anti-Toxocara Seropositivity in the Patients with Eye Diseases in Ophthalmology Clinics in Tehran, Iran

2019 ◽  
Author(s):  
Soodabeh EINIPOUR ◽  
Farid TAHVILDAR BIDEROUNI ◽  
Alireza RAMEZANI
Keyword(s):  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Inflammatory Diseases ◽  
Research Work ◽  
Parasitic Infection ◽  
Toxocara Canis ◽  
Eye Diseases ◽  
Control Group ◽  
Limited Information

Background: Eye diseases, including, Uveitis, inflammation of the retina, and choroid are caused by different agents in humans and has a variety of anterior medial and posterior types. The agent of eye diseases is very different from simple bacterial to acute viral, fungal and parasitic infection. There is limited information regarding the type of eye diseases and Toxocara canis. Methods: Blood samples of 359 individuals (339 patients including endophthalmitis, uveitis, DCR, glaucoma, and cataract 20 individuals as control group) together with their information were collected from ophthalmology hospitals in Tehran, Iran from Feb 2013 to Jan 2015. The patient's serum was evaluated for the presence of anti-Toxocara antibodies by ELISA kits and blood smears for high eosinophilia. The positive samples were confirmed by Western blot analysis for T. canis infection. Results: Overall, 339 patients sera with eye diseases and control group were tested for anti-T. canis antibodies. Nineteen (5.6%) patients had anti-T. canis IgG that 14 (6.1%) were male and 5 (4.5%) were female, and all the patients had negative eosinophilia as well. The results of Western blot analysis for 19 positive patients indicated that 15 were infected by T. canis and 4 were infected by other parasitic infection. The results for control group were negative. Conclusion: All the patients with inflammatory eye diseases such as endophthalmitis, uveitis DCR, glaucoma and cataract were studied for Toxocara infection in this research work were at risk. Therefore, in contrast to the previous idea, all eye inflammatory diseases in ocular patients should be considered for Toxocara antibodies in addition to Uveitis.

Lidocaine Inhibits Ovarian Cancer Cell Proliferation and Induces Apoptosis: An In Vitro Study

2020 ◽  
Vol 10 (5) ◽  
pp. 724-729
Author(s):  
Yaping Xu ◽  
Xiaoqin Fang ◽  
Xianjiang Wei
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Western Blot ◽  
Cancer Cell ◽  
Blot Analysis ◽  
Group Treatment ◽  
Western Blot Analysis ◽  
Ovarian Cancer Cell ◽  
Control Group

Objective: The present study aimed to explore the effects and related mechanism of lidocaine on human ovarian cancer cell lines. Methods: Human ovarian cancer cell lines (SKOV3 and ES-2) were treated with different concentrations of lidocaine for different time. We treated SKOV3 and ES-2 cells using lidocaine then used MTT assay and flow cytometry to detect the cell proliferation and cell apoptosis. In addition, we used western blot analysis to explore the protein expression of Bax and Bcl-2 in SKOV3 and ES-2 cells. Western blot analysis and qRT-PCR were performed for the detection of EMT markers (E-cadherin, N-cadherin). The protein expression levels of TRAF3 and p-p65 in SKOV3 and ES-2 cells were determined by Western blot analysis. Results: Compared to the control group, 0.5, 1, 5, and 10 mM of lidocaine significantly inhibited ovarian cancer cell proliferation at different time points, while 0.1 mM of lidocaine had no significant effect. 1, 5 mM of lidocaine induced the cell apoptosis, and observably reduced expression of Bcl-2 protein, but improved Bax expression markedly compared with the control group. Treatment of lidocaine increased E-cadherin expression, but decreased N-cadherin expression when compared with control group. Treatment of lidocaine increased TRAF3 protein expression, but decreased p-p65 protein expression in ES-2 and SKOV3 cells. Conclusion: We demonstrated that lidocaine inhibited cell proliferation, induced apoptosis, and inhibited EMT in ovarian cancer cells via regulating TRAF3/NF-κB pathway.

scholarly journals Is Oxidative Stress in Mice Brain Regions Diminished by 2-[(2,6-Dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile?

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
A. C. Fortes ◽  
A. A. C. Almeida ◽  
G. A. L. Oliveira ◽  
P. S. Santos ◽  
W. De Lucca Junior ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Brain Regions ◽  
Saline Control ◽  
Control Group ◽  
Nitrite Content

2-[(2,6-Dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile, 5TIO1, is a new 2-aminothiophene derivative with promising pharmacological activities. The aim of this study was to evaluate its antioxidant activity in different areas of mice central nervous system. Male Swiss adult mice were intraperitoneally treated with Tween 80 dissolved in 0.9% saline (control group) and 5TIO1 (0.1, 1, and 10 mg kg−1). Brain homogenates—hippocampus, striatum, frontal cortex, and cerebellum—were obtained after 24 h of observation. Superoxide dismutase and catalase activities, lipid peroxidation and nitrite content were measured using spectrophotometrical methods. To clarify the 5TIO1’s mechanism on oxidative stress, western blot analysis of superoxide dismutase and catalase was also performed. 5TIO1 decreased lipid peroxidation and nitrite content in all brain areas and increased the antioxidant enzymatic activities, specially, in cerebellum. The data of Western blot analysis did not demonstrate evidence of the upregulation of these enzymes after the administration of this compound. Our findings strongly support that 5TIO1 can protect the brain against neuronal damages regularly observed during neuropathologies.

scholarly journals Intermittent Stretching and Osteogenic Differentiation of Bone Marrow Derived Mesenchymal Stem Cells via the p38MAPK-Osterix Signaling Pathway

2015 ◽  
Vol 36 (3) ◽  
pp. 1015-1025 ◽  
Author(s):  
Wen-lin Xiao ◽  
Dai-zun Zhang ◽  
Cun-hui Fan ◽  
Bao-jun Yu
Keyword(s):  
Western Blot ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Mechanical Strain ◽  
Control Group ◽  
Rt Pcr ◽  
Rnai Technology ◽  
P38mapk Signaling

Aims: The relationship between the p38MAPK signaling pathway and osterix in osteogenic differentiation of BMMSCs subjected to intermittent stretching was investigated. Methods: BMMSCs derived from C57BL/6J mice were divided into the following groups: 1) control, 2) stretch, and 3) SB203580+stretch (SB203580 is a p38MAPK signal pathway inhibitor). BMMSCs were exposed to an intermittent mechanical strain of 0.8% (8000μ strain) at 0.5 Hz, twice a day for 30 min each application. BMMSCs were harvested on days 1, 3, and 5 post-treatment. The expression of ALP, COL I, OCN, and osterix mRNA was assessed utilizing RT-PCR while the expression of P-p38MAPK and osterix protein was assessed by Western blot analysis. The osterix gene in mouse BMMSCs was knocked down using RNAi technology and its protein expression was also assessed by Western blot. RT-PCR was used to detect ALP, COL I, and OCN mRNA expression. Results: Intermittent stretching was found to promote expression of ALP, COL I, OCN, and osterix mRNA. Silencing the osterix gene was found to reduce levels of ALP, COL I, and OCN mRNA. Western blot analysis demonstrated that the levels of osterix and P-p38MAPK proteins in the stretch group were significantly higher than in the control group (P<0.05). There was less expression of ALP, COL I, OCN, and osterix mRNA in the SB203580+stretch group than in the control and stretch groups. Conclusions: Data demonstrate that intermittent stretching promotes osteogenic differentiation of BMMSCs, and the p38MAPK-osterix pathway has an important role in the control of osteogenesis-related gene expression.

scholarly journals 2350

2017 ◽  
Vol 1 (S1) ◽  
pp. 8-8
Author(s):  
Dimitri Koutzoumis ◽  
Jose Antonio Pino ◽  
Sharonda S. Harris ◽  
Marisol Quiroz ◽  
Mansour Mohamadzadeh ◽  
...  
Keyword(s):  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Mobile Phase ◽  
Hplc Analysis ◽  
Treated Group ◽  
Control Group ◽  
Tissue Preparation ◽  
Western Blots ◽  
The Impact

OBJECTIVES/SPECIFIC AIMS: Several clinical studies have established a correlation between changes in relative bacterial populations in the gut and Parkinson disease. However, few published experiments have been able to parse out whether these associations are causative or correlative. Our aim is to determine how bacteria in the gut may impact the health and resilience of dopaminergic signaling. Our experiment is designed to serve as a proof-of-principle that controlled alterations to the gut microbiome alters mechanisms in dopamine homeostasis in the midbrain. METHODS/STUDY POPULATION: Bacterial inoculation 8–10-week-old germ-free male mice (C57BL/6) were exclusively used in this experiment. Mice were orally gavaged every 3 days (D0, 3, 6, and 9) with 100 µL novel bacterial suspension (~108 CFU resuspended in PBS with 1.5% NaHCO3) or vehicle and were sacrificed on D11. Tissue preparation—brains were quickly extracted and the striatum was isolated and homogenized in either RIPA buffer with protease inhibitors (for Western blot analysis) or in 0.1 N HClO4 (for HPLC processing). The homogenates were processed through fractional centrifugation to remove cellular debris. Lysate samples were frozen at −80°C until ready for analysis. Protein expression quantification—expression of proteins were measured using intensity of bands from Western blots. Lysates were denatured prior to loading with LB with 10% β-mercaptoethanol and 30-minute incubation at 37°C. All immunoblots were normalized to immunoreactivity to α-tubulin. Immunoblot intensity was determined using the ImageJ software. Dopamine/dopamine metabolite quantification HPLC analysis was used to determine dopamine and dopamine metabolite concentration. Aliquots of the lysate were injected onto a C18 column using a mobile phase consisting of 50 mM H2NaO4P·H2O, 0.72 mM sodium octyl sulfate, 75 µM Na2 EDTA, and 10% acetonitrile (pH 3.0). The mobile phase was pumped through the system at 0.3 mL/minute. RESULTS/ANTICIPATED RESULTS: Measured total dopamine concentration through HPLC analysis in the striatum showed no significant differences in the bacteria-treated group relative to the control group. The metabolites DOPAC and HVA had an elevated measured concentration in the bacteria-treated group relative to the control group. Western blot analysis showed decreased immunoreactivity for DAT and TH in the bacteria-treated group compared with the control group. There was no significance difference in the immunoreactivity for VMAT2. DISCUSSION/SIGNIFICANCE OF IMPACT: This study demonstrates that dopamine signaling dynamics in the midbrain can be altered by changes in the gut flora in mice. These results further substantiate the impact of the gut-brain axis and may even point to a potential avenue of bolstering the resilience of dopaminergic neurons in preventing the onset of PD. Further experiments must be performed to understand the mechanism of the observed changes and to determine if these changes have any salutary effect.

scholarly journals EA Ameliorated Depressive Behaviors in CUMS Rats and Was Related to Its Suppressing Autophagy in the Hippocampus

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Zhinan Zhang ◽  
Xiaowen Cai ◽  
Zengyu Yao ◽  
Feng Wen ◽  
Zhiyi Fu ◽  
...  
Keyword(s):  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Preference Test ◽  
Control Group ◽  
Mild Stress ◽  
Sprague Dawley ◽  
Transmission Electron ◽  
Nonsignificant Difference ◽  
Sucrose Preference Test

Autophagy is confirmed to be involved in the onset and development of depression, and some antidepressants took effect by influencing the autophagic process. Electroacupuncture (EA), as a common complementary treatment for depression, may share the mechanism of influencing autophagy in the hippocampus like antidepressants. To investigate that, sixty Sprague-Dawley rats firstly went through chronic unpredictable mild stress (CUMS) model establishment, and 15 rats were assigned to a control group. After modeling, 45 successfully CUMS-induced rats were randomly divided to 3 groups: CUMS, selective serotonin reuptake inhibitor (SSRI), and EA groups (15 rats per group), to accept different interventions for 2 weeks. A sucrose preference test (SPT), weighing, and open field test (OFT) were measurement for depressive behaviors of rats. Transmission electron microscope (TEM), immunohistochemistry (IHC), and western blot analysis were used to evaluate the autophagic changes. After that, depression-like behaviors were successfully induced in CUMS models and reversed by SSRI and EA treatments (both p<0.05), but these two therapies had nonsignificant difference between each other (p>0.05). Autolysosomes observed through TEM in the CUMS group were more than that in the control group. Their number and size in the SSRI and EA groups also decreased significantly. From IHC, the CUMS group showed enhanced positive expression of both Beclin1 and LC3 in CA1 after modeling (p<0.05), and the LC3 level declined after EA treatments, which was verified by decreased LC3-II/LC3-I in western blot analysis. We speculated that CUMS-induced depression-like behavior was interacted with an autophagy process in the hippocampus, and EA demonstrated antidepressant effects by partly inhibiting autophagy with a decreased number of autolysosomes and level of LC3 along with LC3-II/LC3-I.

Protein Microarray Analysis of Nasal Polyps from Aspirin-Sensitive and Aspirin-Tolerant Patients with Chronic Rhinosinusitis

2009 ◽  
Vol 23 (3) ◽  
pp. 268-272 ◽  
Author(s):  
Kelly A. Zander ◽  
Milene T. Saavedra ◽  
James West ◽  
Victor Scapa ◽  
Linda Sanders ◽  
...  
Keyword(s):  
Protein Expression ◽  
Western Blot ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyp ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Nasal Polyps ◽  
Protein Microarray ◽  
Control Group ◽  
Microarray Technology

Background The purpose of this study was to apply protein microarray technology to the study of sinonasal tissue and to identify differential protein expression in nasal polyps from aspirin-sensitive (AS) versus aspirin-tolerant (AT) patients with chronic rhinosinusitis (CRS) and CRS with nasal polyps (CRSwNPs). Methods Nasal polyp specimens were prospectively obtained from two groups of patients with CRSwNP. The test group (AS) consisted of five patients that were diagnosed with CRSwNP and intolerance to aspirin based on medical history and physical exam. The control group (AT) consisted of four AT patients with CRSwNP. Protein was extracted and labeled from harvested polyps and the Sigma Panorama Antibody Microarray–Cell Signaling Kit was used to identify differences in protein expression between the two polyp groups. Western blot analysis was used to validate the results of the protein microarray. Results The protein microarray showed a greater than twofold change in expression of both beta-adaptin and heat shock protein 70 (HSP70). Western blot analysis confirmed up-regulation of beta-adaptin and HSP70 in nasal polyp tissue from AS patients. Conclusion Pooled samples of AS and AT nasal polyps evaluated by protein microarray show distinct protein expression profiles in the stress response and receptor-mediated endocytosis pathways. This study establishes the successful application of protein microarray technology to study nasal polyposis, which in turn can be validated by Western blot analysis.

Lidocaine Protects Endometriosis by Inducing Apoptosis of Endometrial Stromal Cells

2020 ◽  
Vol 10 (6) ◽  
pp. 845-851
Author(s):  
Ping Li ◽  
Qian Zhang ◽  
Tao Li ◽  
Haibo Wang ◽  
Xia Ji ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Stromal Cells ◽  
Blot Analysis ◽  
Protein Level ◽  
Cell Apoptosis ◽  
Western Blot Analysis ◽  
Control Group ◽  
Endometrial Stromal Cells ◽  
Qrt Pcr

Objective: This study aimed to explore the effects of lidocaine on ectopic endometrial stromal cells and the underlying mechanisms in endometriosis. Methods: Ectopic endometrial stromal cells (ESCs), which were separated from endometriotic tissues, were subjected to various concentrations of lidocaine for different time. After the treatment of lidocaine, MTT assay was applied to assess the cell proliferation of ESCs, and cell apoptosis was analyzed by flow cytometry. Meanwhile, we detected the protein level of pro-caspse3 and cleaved-caspase3 protein in ESCs by Western blot analysis. The invasion and migration capability of ESCs was also detected by transwell assay. Western blot analysis and qRT-PCR were performed for the detection of EMT markers (E-cadherin, N-cadherin and MMP-9). Similarly, the expression levels of β-catenin, cyclin D1 and c-myc in ESCs were determined by Western blot analysis and qRT-PCR. Results: 0.5, 1, 5 and 10 mM of lidocaine obviously inhibited the cell proliferation of ESCs at different time points compared with the control group, while no significant effect was observed in 0.1 mM lidocaine treated cells. Lidocaine dose-dependently increased cell apoptosis, reduced the protein level of pro-caspse3 protein, but improved cleaved-caspase3 protein level in ESCs. Moreover, lidocaine dose-dependently decreased the migration and invasion capabilities of ESCs. In addition, compared to the control group, lidocaine enhanced the level of E-cadherin, and reduced the level of N-cadherin and MMP-9 in ESCs. Lidocaine suppressed the level of β-catenin, cyclin D1 and c-myc in ESCs in a dose-dependent manner. Conclusion: We demonstrated that lidocaine protected endometriosis by inducing the apoptosis of ESCs via regulating Wnt/β-catenin pathway.

O-218 The effect of mTOR activation on human primordial follicle activation during in-situ culture

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Z Ghezelayagh ◽  
N Abtahi ◽  
M. Rezazadeh Valojerdi ◽  
B Ebrahimi
Keyword(s):  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Culture Medium ◽  
Primordial Follicle ◽  
Control Group ◽  
Primordial Follicles ◽  
Primordial Follicle Activation ◽  
Follicle Activation

Abstract Study question What is the effect of mTOR pathway activation on human primordial follicles in-situ activation and subsequent development following tissue cryopreservation? Summary answer Temporary treatment of cryopreserved human ovarian tissue with mTOR activators cause the initiation of primordial follicle development and influence steroidogenesis. What is known already In-vitro activation of primordial follicles to produce mature oocytes provides an alternative technique for fertility preservation. The employment of different stimulators of PI3K pathway has been successfully used to activate resting follicles during culture or prior to grafting in patients with premature ovarian insufficiency. The addition of phosphatidic acid (PA) and propranolol (PP), as mTOR stimulators, in the culture medium has promoted primordial follicle activation morphologically in mouse and human ovaries. Molecular and functional evaluations of primordial follicle activation after treatment with the mentioned stimulators has not been conducted. Study design, size, duration Ovarian tissues which were donated from 6 transsexual patients (23-35 years old), were dissected and cryopreserved with slow-freezing technique. After thawing, they were cut into 1x1x1 mm fragments and incubated with different stimulators in three groups: 1) Control (without stimulators), 2) PA (200µM), and 3) PA+PP (200µM & 50µM respectively). In groups two and three, ovarian fragments were cultured for 24 hours in presence of stimulators and then cultured for additional 6 days without stimulators. Participants/materials, setting, methods The cultured ovarian fragments were directly processed for Hematoxylin and Eosin staining and Western blot analysis. The proportion of morphologically normal and degenerated primordial and growing follicles and 17β-estradiol (E2) level in the culture medium were compared after 1 and 7 days of culture to assess follicular development and function. Western blot analysis for phosphorylated and non-phosphorylated status of FOXO3a and RSP6 proteins expression were compared after 24 hours of incubation. Main results and the role of chance The proportion of primordial and growing follicles were not significantly different in the experimental groups after 24 hours of incubation with either of the stimulators. Western blot analyses indicated a significant reduction of FOXO3a in the PA+PP group compared to the control group. The phosphorylation level of RPS6 protein did not significantly change in either of the groups. The proportion of transitional follicles were significantly higher in the PA group compared to other groups after 7 days of culture. The E2 secretion level was significantly higher at the last day of culture compared to day 1 for all groups. At the end of the culture period, E2 levels was significantly higher in both PA and PA+PP groups compared to the control group. Limitations, reasons for caution Due to ovarian fragmentation before culture, the HIPPO pathway downstream molecules should have also been evaluated by western blot, which was not contributed in this study. Wider implications of the findings The results demonstrate the beneficial effect of mTOR signaling to accelerate early primordial follicle recruitment in cryopreserved-thawed human ovarian fragments. Trial registration number not applicable

Radiosensitivity of glioma to Gamma Knife treatment enhanced in vitro and in vivo by RNA interfering Ku70 that is mediated by a recombinant adenovirus

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 228-235 ◽  
Author(s):  
Qiang Jia ◽  
Yanhe Li ◽  
Desheng Xu ◽  
Zhenjiang Li ◽  
Zhiyuan Zhang ◽  
...  
Keyword(s):  
Western Blot ◽  
Gamma Knife ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Glioma Cells ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
C6 Cells

Object The authors sought to evaluate modification of the radiation response of C6 glioma cells in vitro and in vivo by inhibiting the expression of Ku70. To do so they investigated the effect of gene transfer involving a recombinant replication-defective adenovirus containing Ku70 short hairpin RNA (Ad-Ku70shRNA) combined with Gamma Knife treatment (GKT). Methods First, Ad-Ku70shRNA was transfected into C6 glioma cells and the expression of Ku70 was measured using Western blot analysis. In vitro, phenotypical changes in C6 cells, including proliferation, cell cycle modification, invasion ability, and apoptosis were evaluated using the MTT (3′(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, Western blot analysis, and cell flow cytometry. In vivo, parental C6 cells transfected with Ad-Ku70shRNA were implanted stereotactically into the right caudate nucleus in Sprague-Dawley rats. After GKS, apoptosis was analyzed using the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) method. The inhibitory effects on growth and invasion that were induced by expression of proliferating cell nuclear antigen and matrix metalloproteinase–9 were determined using immunohistochemical analyses. Results The expression of Ku70 was clearly inhibited in C6 cells after transfection with Ad-Ku70shRNA. In vitro following transfection, the C6 cells showed improved responses to GKT, including suppression of proliferation and invasion as well as an increased apoptosis index. In vivo following transfection of Ad-Ku70shRNA, the therapeutic efficacy of GKT in rats with C6 gliomas was greatly enhanced and survival times in these animals were prolonged. Conclusions Our data support the potential for downregulation of Ku70 expression in enhancing the radiosensitivity of gliomas. The findings of our study indicate that targeted gene therapy–mediated inactivation of Ku70 may represent a promising strategy in improving the radioresponsiveness of gliomas to GKT.

Synthesis and Characterization of Quinoline-3-Carboxamide Derivatives as Inhibitors of the ATM Kinase

2020 ◽  
Vol 20 (23) ◽  
pp. 2070-2079
Author(s):  
Srimadhavi Ravi ◽  
Sugata Barui ◽  
Sivapriya Kirubakaran ◽  
Parul Duhan ◽  
Kaushik Bhowmik
Keyword(s):  
Western Blot ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Cancer Cell Lines ◽  
Atm Kinase ◽  
Cytotoxicity Studies

Background: The importance of inhibiting the kinases of the DDR pathway for radiosensitizing cancer cells is well established. Cancer cells exploit these kinases for their survival, which leads to the development of resistance towards DNA damaging therapeutics. Objective: In this article, the focus is on targeting the key mediator of the DDR pathway, the ATM kinase. A new set of quinoline-3-carboxamides, as potential inhibitors of ATM, is reported. Methods: Quinoline-3-carboxamide derivatives were synthesized and cytotoxicity assay was performed to analyze the effect of molecules on different cancer cell lines like HCT116, MDA-MB-468, and MDA-MB-231. Results: Three of the synthesized compounds showed promising cytotoxicity towards a selected set of cancer cell lines. Western Blot analysis was also performed by pre-treating the cells with quercetin, a known ATM upregulator, by causing DNA double-strand breaks. SAR studies suggested the importance of the electron-donating nature of the R group for the molecule to be toxic. Finally, Western-Blot analysis confirmed the down-regulation of ATM in the cells. Additionally, the PTEN negative cell line, MDA-MB-468, was more sensitive towards the compounds in comparison with the PTEN positive cell line, MDA-MB-231. Cytotoxicity studies against 293T cells showed that the compounds were at least three times less toxic when compared with HCT116. Conclusion: In conclusion, these experiments will lay the groundwork for the evolution of potent and selective ATM inhibitors for the radio- and chemo-sensitization of cancer cells.

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