Systematical identification of cell-specificity of CTCF-gene binding based on epigenetic modifications

Abstract The CCCTC-binding factor (CTCF) mediates transcriptional regulation and implicates epigenetic modifications in cancers. However, the systematically unveiling inverse regulatory relationship between CTCF and epigenetic modifications still remains unclear, especially the mechanism by which histone modification mediates CTCF binding. Here, we developed a systematic approach to investigate how epigenetic changes affect CTCF binding. Through integration analysis of CTCF binding in 30 cell lines, we concluded that CTCF generally binds with higher intensity in normal cell lines than that in cancers, and higher intensity in genome regions closed to transcription start sites. To facilitate the better understanding of their associations, we constructed linear mixed-effect models to analyze the effects of the epigenetic modifications on CTCF binding in four cancer cell lines and six normal cell lines, and identified seven epigenetic modifications as potential epigenetic patterns that influence CTCF binding intensity in promoter regions and six epigenetic modifications in enhancer regions. Further analysis of the effects in different locations revealed that the epigenetic regulation of CTCF binding was location-specific and cancer cell line-specific. Moreover, H3K4me2 and H3K9ac showed the potential association with immune regulation of disease. Taken together, our method can contribute to improve the understanding of the epigenetic regulation of CTCF binding and provide potential therapeutic targets for treating tumors associated with CTCF.

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New Chitosan Polymer Scaffold Schiff Bases as Potential Cytotoxic Activity: Synthesis, Molecular Docking, and Physiochemical Characterization

Frontiers in Chemistry ◽

10.3389/fchem.2021.796599 ◽

2022 ◽

Vol 9 ◽

Author(s):

Ponnusamy Packialakshmi ◽

Perumal Gobinath ◽

Daoud Ali ◽

Saud Alarifi ◽

Raman Gurusamy ◽

...

Keyword(s):

Binding Affinity ◽

Schiff Bases ◽

Cell Lines ◽

Cancer Cell ◽

Normal Cell ◽

Cancer Cell Line ◽

Chitosan Derivatives ◽

Highly Active ◽

Low Cytotoxicity ◽

Mcf 7

In this work, we synthesize the sulfonated Schiff bases of the chitosan derivatives 2a-2j without the use of a catalyst in two moderately straightforward steps with good yield within a short reaction time. The morphology and chemical structure of chitosan derivatives were investigated using FT-IR, NMR (1H—13C), XRD, and SEM. Furthermore, our chitosan derivatives were tested for their anticancer activity against the MCF-7 cancer cell line, and doxorubicin was used as a standard. In addition, the normal cell lines of the breast cancer cell MCF-10A, and of the lung cell MRC-5 were tested. Compound 2 h, with a GI50 value of 0.02 µM for MCF-7, is highly active compared with the standard doxorubicin and other compounds. The synthesized compounds 2a-2j exhibit low cytotoxicity, with IC50 > 100 μg/ml, against normal cell lines MCF-10A, MRC-5. We also provide the results of an in-silico study involving the Methoxsalen protein (1Z11). Compound 2h exhibits a higher binding affinity for 1Z11 protein (−5.9 kcal/mol) and a lower binding affinity for Doxorubicin (−5.3 kcal/mol) than certain other compounds. As a result of the aforementioned findings, the use of compound 2h has an anticancer drug will be researched in the future.

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Effect crude aquatic extract of leaves Ocimum basilicum on caner and normal cell lines in vitro

Journal of Biotechnology Research Center ◽

10.24126/jobrc.2013.7.1.233 ◽

2013 ◽

Vol 7 (1) ◽

pp. 5-13

Author(s):

Israa Sekar Salmman

Keyword(s):

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Crude Extract ◽

Normal Cell ◽

Cancer Cell Line ◽

Inhibitory Effect ◽

Ocimum Basilicum ◽

High Concentration

Leaves of Ocimum basilicum were extracted with distilled water to prepare aquatic crude extract, five concentration from this extract (1000, 500, 250, 125, 62.5)µg/ml were used to study the effect of extract on cancer cell lines(Larynex carcinoma hep-2, cervix carcinoma Hela and mammary gland adenocarcinoma AMN-3) and the time exposure 24 and 48 hours as well as the effect of aquous extract on normal cell line for embryonic mice fibroblast(MEF) was studied in vitro at 48hrs. exposure. The result showed that aqueous crude extract of Ocimum basilicum leaves has different effects on cancer cell lines with significante p<0.05 the high concentration 1000 µg/ml has more inhibitory effect on cancer cell line Hep-2 compared with low concentration at 24and 48 hrs.while the Hela cancer cell line has hormetic effect which recognized by contrast in low concentration inhibitory effect as compared with high concentration at 24 and 48 hr.that low ones inhibit cell proliferation while in high ones cell proliferation continue, but AMN-3 cancer cell line more affected by low concentrations from high concentrations. Normal cell line show no significant effect for all concentrations used of aquatic crude extract of Ocimum basilicum leaf except 62.5 µg/ml with high cell inhibition 16%.

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Synthesis, Anticancer Activity on Prostate Cancer Cell Lines and Molecular Modeling Studies of Flurbiprofen-Thioether Derivatives as Potential Target of MetAP (Type II)

Medicinal Chemistry ◽

10.2174/1573406415666190613162322 ◽

2020 ◽

Vol 16 (6) ◽

pp. 735-749 ◽

Cited By ~ 1

Author(s):

Özgür Yılmaz ◽

Burak Bayer ◽

Hatice Bekçi ◽

Abdullahi I. Uba ◽

Ahmet Cumaoğlu ◽

...

Keyword(s):

Prostate Cancer ◽

Molecular Modeling ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Prostate Cancer Cell Lines ◽

Molecular Modeling Studies

Background:: Prostate cancer is still one of the serious causes of mortality and morbidity in men. Despite recent advances in anticancer therapy, there is a still need of novel agents with more efficacy and specificity in the treatment of prostate cancer. Because of its function on angiogenesis and overexpression in the prostate cancer, methionine aminopeptidase-2 (MetAP-2) has been a potential target for novel drug design recently. Objective:: A novel series of Flurbiprofen derivatives N-(substituted)-2-(2-(2-fluoro-[1,1'- biphenyl]-4-il)propanoyl)hydrazinocarbothioamide (3a-c), 4-substituted-3-(1-(2-fluoro-[1,1'-biphenyl]- 4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione (4a-d), 3-(substitutedthio)-4-(substituted-phenyl)- 5-(1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethyl)-4H-1,2,4-triazole (5a-y) were synthesized. The purpose of the research was to evaluate these derivatives against MetAP-2 in vitro and in silico to obtain novel specific and effective anticancer agents against prostate cancer. Methods: The chemical structures and purities of the compounds were defined by spectral methods (1H-NMR, 13C-NMR, HR-MS and FT-IR) and elemental analysis. Anticancer activities of the compounds were evaluated in vitro by using MTS method against PC-3 and DU-143 (androgenindependent human prostate cancer cell lines) and LNCaP (androgen-sensitive human prostate adenocarcinoma) prostate cancer cell lines. Cisplatin was used as a positive sensitivity reference standard. Results:: Compounds 5b and 5u; 3c, 5b and 5y; 4d and 5o showed the most potent biological activity against PC3 cancer cell line (IC50= 27.1 μM, and 5.12 μM, respectively), DU-145 cancer cell line (IC50= 11.55 μM, 6.9 μM and 9.54 μM, respectively) and LNCaP cancer cell line (IC50= 11.45 μM and 26.91 μM, respectively). Some compounds were evaluated for their apoptotic caspases protein expression (EGFR/PI3K/AKT pathway) by Western blot analysis in androgen independent- PC3 cells. BAX, caspase 9, caspsase 3 and anti-apoptotic BcL-2 mRNA levels of some compounds were also investigated. In addition, molecular modeling studies of the compounds on MetAP-2 enzyme active site were evaluated in order to get insight into binding mode and energy. Conclusion:: A series of Flurbiprofen-thioether derivatives were synthesized. This study presented that some of the synthesized compounds have remarkable anticancer and apoptotic activities against prostate cancer cells. Also, molecular modeling studies exhibited that there is a correlation between molecular modeling and anticancer activity results.

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Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2-Thioxoimidazolidinones

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666171129213838 ◽

2018 ◽

Vol 18 (4) ◽

pp. 573-582 ◽

Cited By ~ 1

Author(s):

Khaled R.A. Abdellatif ◽

Mostafa M. Elbadawi ◽

Mohammed T. Elsaady ◽

Amer A. Abd El-Hafeez ◽

Takashi Fujimura ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Topoisomerase I ◽

Cancer Cell Line ◽

Cytotoxic Agents ◽

Dependent Manner ◽

Human Lung Fibroblast ◽

Mcf 7

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.

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Design, Synthesis, Molecular Docking, and Anticancer Evaluation of Pyrazole Linked Pyrazoline Derivatives with Carbothioamide Tail as EGFR Kinase Inhibitors

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200727093613 ◽

2020 ◽

Vol 21 (1) ◽

pp. 42-60

Author(s):

Farah Nawaz ◽

Ozair Alam ◽

Ahmad Perwez ◽

Moshahid A. Rizvi ◽

Mohd. Javed Naim ◽

...

Keyword(s):

Molecular Docking ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Kinase Assay ◽

Cervix Uteri ◽

Egfr Kinase

Background: The Epidermal Growth Factor Receptor (known as EGFR) induces cell differentiation and proliferation upon activation through the binding of its ligands. Since EGFR is thought to be involved in the development of cancer, the identification of new target inhibitors is the most viable approach, which recently gained momentum as a potential anticancer therapy. Objective: To assess various pyrazole linked pyrazoline derivatives with carbothioamide for EGFR kinase inhibitory as well as anti-proliferative activity against human cancer cell lines viz. A549 (non-small cell lung tumor), MCF-7 (breast cancer cell line), SiHa (cancerous tissues of the cervix uteri), and HCT-116 (colon cancer cell line). Methods: In vitro EGFR kinase assay, in vitro MTT assay, Lactate dehydrogenase release, nuclear staining (DAPI), and flow cytometry cell analysis. Results: Compounds 6h and 6j inhibited EGFR kinase at concentrations of 1.66μM and 1.9μM, respectively. Furthermore, compounds 6h and 6j showed the most potent anti-proliferative results against the A549 KRAS mutation cell line (IC50 = 9.3 & 10.2μM). Through DAPI staining and phase contrast microscopy, it was established that compounds 6h and 6j also induced apoptotic activity in A549 cells. This activity was further confirmed by FACS using Annexin-V-FITC and Propidium Iodide (PI) labeling. Molecular docking studies performed on 6h and 6j suggested that the compounds can bind to the hinge region of ATP binding site of EGFR tyrosine kinase in a similar pose as that of the standard drug gefitinib. Conclusion: The potential anticancer activity of compounds 6h and 6j was confirmed and need further exploration in cancer cell lines of different tissue origin and signaling pathways, as well as in animal models of cancer development.

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Bimetallic Iron–Palladium Catalyst System as a Lewis-Acid for the Synthesis of Novel Pharmacophores Based Indole Scaffold as Anticancer Agents

Molecules ◽

10.3390/molecules26082212 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2212

Author(s):

Mohammad Shahidul Islam ◽

M. Ali ◽

Abdullah Mohammed Al-Majid ◽

Abdullah Saleh Alamary ◽

Saeed Alshahrani ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Palladium Catalyst ◽

Cancer Cell Line ◽

Catalyst System ◽

Mcf 7 ◽

Iron Palladium

The Friedel–Crafts reaction between substituted indoles as nucleophiles with chalcones-based benzofuran and benzothiophene scaffolds was carried out by employing a highly efficient bimetallic iron–palladium catalyst system. This catalytic approach produced the desired bis-heteroaryl products with low catalyst loading, a simple procedure, and with acceptable yield. All synthesized indole scaffolds 3a–3s were initially evaluated for their cytotoxic effect against human fibroblast BJ cell lines and appeared to be non-cytotoxic. All non-cytotoxic compounds 3a–3s were then evaluated for their anticancer activities against cervical cancer HeLa, prostate cancer PC3, and breast cancer MCF-7 cell lines, in comparison to standard drug doxorubicin, with IC50 values 1.9 ± 0.4 µM, 0.9 ± 0.14 µM and 0.79 ± 0.05 µM, respectively, and appeared to be moderate to weak anticancer agents. Fluoro-substituted chalcone moiety-containing compounds, 3b appeared to be the most active member of the series against cervical HeLa (IC50 = 8.2 ± 0.2 µM) and breast MCF-7 cancer cell line (IC50 = 12.3 ± 0.04 µM), whereas 6-fluroindol-4-bromophenyl chalcone-containing compound 3e (IC50 = 7.8 ± 0.4 µM) appeared to be more active against PC3 prostate cancer cell line.

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Antiproliferative effect of rosehip tea phenolics in prostate cancer cell lines

Turkish Journal of Biochemistry ◽

10.1515/tjb-2019-0262 ◽

2020 ◽

Vol 45 (4) ◽

pp. 423-428

Author(s):

Ali Mert Özgönül ◽

Aycan Aşık ◽

Burak Durmaz ◽

Ramin Aslaminabad ◽

Cumhur Gündüz ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Lncap Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Line ◽

Prostate Cancer Cell Line ◽

Antiproliferative Effect ◽

Natural Sources

AbstractObjectivesRecently, phenolic compounds (quercetin, kaempferol, ellagic acid (EA), and myricetin) as natural sources have been suggested to be used for treatment and chemoprevention of prostate cancer. Since rosehip includes the above molecules in high concentration, we set out to investigate possible anti-proliferative effect of rosehip tea on the prostate cancer cell line.MethodsThe flavonol content of rosehip tea prepared at different temperatures and time intervals was determined first and then the antiproliferative effect of tea samples was established by adding tea samples to the prostate cancer cell line (VCaP and LNCaP).ResultsQuercetin was more effective in LNCaP cell than in VCaP cell (IC50 = 20 and 200 μM, respectively). The boiled fruit shredded at minute 7 showed the highest levels of quercetin, EA and kaempferol and the boiled fruit at minute 7 had the highest levels of kaempferol and EA. The tea samples were prepared in concentrations relevant to their IC50 values, added to the VCaP and LNCaP cell lines. The antiproliferative effect of rosehip tea on VCaP cells was slightly greater than that of LNCaP cells.ConclusionEach of the flavonols exhibits an antiproliferative effect. Our data clearly indicated that rosehip as a natural source of all flavonols had an antiproliferative effect on androgen-sensitive prostate cancer. Now that it is important to use natural sources in cancer, rosehip seems to be a promising natural product to be used to treat the prostate illness.

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Synthesis, Characterization and Biological Evaluation of Metal Adamantyl 2-Pyridylhydrazone Complexes

Molecules ◽

10.3390/molecules25112530 ◽

2020 ◽

Vol 25 (11) ◽

pp. 2530

Author(s):

Ihsan A. Shehadi ◽

Fatima-Azzahra Delmani ◽

Areej M. Jaber ◽

Hana Hammad ◽

Murad A. AlDamen ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Line ◽

Direct Methods ◽

Cancer Cell Lines ◽

Biological Evaluation ◽

Colorectal Cancer Cell Line ◽

Breast Cancer Cell Lines ◽

Human Cancer Cell Lines

Four new complexes derived from adamantly containing hydrazone (APH) ligand with Cu(II) (1), Co(II) (2), Ni(II) (3) and Zn(II) (4), have been synthesized and characterized using different physicochemical methods. The structure of the ligand APH and its copper complex 1 have been established by single-crystal X-ray diffraction direct methods, which reveal that complex 1 has distorted square-pyramidal geometry. Complexes 1–4 are screened against seven human cancer cell lines namely, breast cancer cell lines (MCF7, T47D, MDA-MB-231), prostate cancer cell lines (PC3, DU145) and the colorectal cancer cell line Coco-2, for their antiproliferative activities. Complex 1 has shown a promising anticancer activity compared to the other ones. The structural and spectroscopic analysis of APH and its complexes are confirmed by DFT calculations.

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Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening

SLAS DISCOVERY Advancing Life Sciences ◽

10.1177/2472555219873068 ◽

2019 ◽

Vol 25 (1) ◽

pp. 9-20 ◽

Cited By ~ 2

Author(s):

Olivia W. Lee ◽

Shelley Austin ◽

Madison Gamma ◽

Dorian M. Cheff ◽

Tobie D. Lee ◽

...

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

High Throughput ◽

High Throughput Screening ◽

Drug Targets ◽

Large Scale ◽

Early Stage ◽

Cancer Cell Line ◽

Hek 293 ◽

Cytotoxic Compounds

Cell-based phenotypic screening is a commonly used approach to discover biological pathways, novel drug targets, chemical probes, and high-quality hit-to-lead molecules. Many hits identified from high-throughput screening campaigns are ruled out through a series of follow-up potency, selectivity/specificity, and cytotoxicity assays. Prioritization of molecules with little or no cytotoxicity for downstream evaluation can influence the future direction of projects, so cytotoxicity profiling of screening libraries at an early stage is essential for increasing the likelihood of candidate success. In this study, we assessed the cell-based cytotoxicity of nearly 10,000 compounds in the National Institutes of Health, National Center for Advancing Translational Sciences annotated libraries and more than 100,000 compounds in a diversity library against four normal cell lines (HEK 293, NIH 3T3, CRL-7250, and HaCat) and one cancer cell line (KB 3-1, a HeLa subline). This large-scale library profiling was analyzed for overall screening outcomes, hit rates, pan-activity, and selectivity. For the annotated library, we also examined the primary targets and mechanistic pathways regularly associated with cell death. To our knowledge, this is the first study to use high-throughput screening to profile a large screening collection (>100,000 compounds) for cytotoxicity in both normal and cancer cell lines. The results generated here constitute a valuable resource for the scientific community and provide insight into the extent of cytotoxic compounds in screening libraries, allowing for the identification and avoidance of compounds with cytotoxicity during high-throughput screening campaigns.

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