scholarly journals Integrated evaluation of telomerase activation and telomere maintenance across cancer cell lines

2021 ◽  
Author(s):  
Kevin Hu ◽  
Mahmoud Ghandi ◽  
Franklin W. Huang
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Mutant Cell ◽  
Leukemia Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Telomere Maintenance ◽  
Specific Expression ◽  
Allele Specific ◽  
Telomere Regulation

AbstractIn cancer, telomere maintenance is critical for the development of replicative immortality. Using genome sequences from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer Project, we calculated telomere content across 1,299 cancer cell lines. We find that telomerase reverse transcriptase (TERT) expression correlates with telomere content in lung, central nervous system, and leukemia cell lines. Using CRISPR/Cas9 screening data, we show that lower telomeric content is associated with dependency of CST telomere maintenance components. Increased dependencies of shelterin members are associated with wild-type TP53 status. Investigating the epigenetic regulation of TERT, we find widespread allele-specific expression in promoter-wildtype contexts. TERT promoter-mutant cell lines exhibit hypomethylation at PRC2-repressed regions, suggesting a cooperative global epigenetic state in the reactivation of telomerase. By incorporating telomere content with genomic features across comprehensively characterized cell lines, we provide further insights into the role of telomere regulation in cancer immortality.

scholarly journals Integrated evaluation of telomerase activation and telomere maintenance across cancer cell lines

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kevin Hu ◽  
Mahmoud Ghandi ◽  
Franklin W Huang
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Mutant Cell ◽  
Leukemia Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Telomere Maintenance ◽  
Specific Expression ◽  
Allele Specific ◽  
Telomere Regulation

In cancer, telomere maintenance is critical for the development of replicative immortality. Using genome sequences from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer Project, we calculated telomere content across 1,299 cancer cell lines. We find that telomerase reverse transcriptase (TERT) expression correlates with telomere content in lung, central nervous system, and leukemia cell lines. Using CRISPR/Cas9 screening data, we show that lower telomeric content is associated with dependency of CST telomere maintenance genes. Increased dependencies of shelterin members are associated with wild-type TP53 status. Investigating the epigenetic regulation of TERT, we find widespread allele-specific expression in promoter-wildtype contexts. TERT promoter-mutant cell lines exhibit hypomethylation at PRC2-repressed regions, suggesting a cooperative global epigenetic state in the reactivation of telomerase. By incorporating telomere content with genomic features across comprehensively characterized cell lines, we provide further insights into the role of telomere regulation in cancer immortality.

scholarly journals Post-perturbational transcriptional signatures of cancer cell line vulnerabilities

2020 ◽  
Author(s):  
Andrew Jones ◽  
Aviad Tsherniak ◽  
James M. McFarland
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Large Scale ◽  
Cancer Cell Line ◽  
Cellular Responses ◽  
Cancer Cell Lines ◽  
Transcriptional Responses ◽  
Specific Expression ◽  
Transcriptional Signature

AbstractWhile chemical and genetic viability screens in cancer cell lines have identified many promising cancer vulnerabilities, simple univariate readouts of cell proliferation fail to capture the complex cellular responses to perturbations. Complementarily, gene expression profiling offers an information-rich measure of cell state that can provide a more detailed account of cellular responses to perturbations. Relatively little is known, however, about the relationship between transcriptional responses to per-turbations and the long-term cell viability effects of those perturbations. To address this question, we integrated thousands of post-perturbational transcriptional profiles from the Connectivity Map with large-scale screens of cancer cell lines’ viability response to genetic and chemical perturbations. This analysis revealed a generalized transcriptional signature associated with reduced viability across perturbations, which was consistent across post-perturbation time-points, perturbation types, and viability datasets. At a more granular level, we lay out the landscape of treatment-specific expression-viability relationships across a broad panel of drugs and genetic reagents, and we demonstrate that these post-perturbational expression signatures can be used to infer long-term viability. Together, these results help unmask the transcriptional changes that are associated with perturbation-induced viability loss in cancer cell lines.

scholarly journals Evaluation of Anticancer Action of Martynia annua Linn Root Extract on Different Human Cancer Cell Lines

2021 ◽  
pp. 96-109
Author(s):  
Rahul Kumar Gupta ◽  
Renu Bharat Rathi
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Leukemia Cell ◽  
Cancer Cell Line ◽  
Ethanolic Extract ◽  
Cancer Cell Lines ◽  
Leukemia Cell Line ◽  
Human Leukemia ◽  
Human Leukemia Cell Line

Background: In the last few decades, plants have been playing a vital role in treating cancer and infectious diseases. Natural products have been rediscovered as effective methods of drug production amid advances in combinatorial chemistry. Roots of Martynia annua are being used as a folklore remedy for the treatment of cancer and rheumatism successfully. Aims of the Study: In the present study, ethanolic, aqueous and hydro-ethanolic root extracts of Martynia annua were screened for in vitro cytotoxicity activity using different cell lines. Settings and Design: In the experiment, lung cancer cell lines (A549), leukemia cancer cell lines (K562), oral cancer cell lines (SCC-40), breast cancer cell lines (MCF-7) & cervix cancer cell lines (SiHa) were studied on the extracts. Materials and Methods: The method used was Sulforhodamine B (SRB) assay technique in which growth inhibition of 50% (GI50) was analyzed by comparing it with standard drug Adriamycin (ADR) (doxorubicin). Results: Aqueous & ethanolic extract of Martynia annua root had shown high anticancer activity with GI50 value 11.3µg/ml and 20.4µg/ml respectively on human leukemia cell line K-562 but for human breast cancer cell line MCF-7, human lung cancer cell line A-549, human squamous cell carcinoma SCC-40 and human cervical cancer cell line SiHa the extracts showed activity in more than 80µg/ml. Conclusion: The anticancer activity of aqueous extract of Martynia annua root was found superior than the ethanolic extract in Human Leukemia Cell Line K-562. The study indicates that the Martynia annua root extracts are most effective against the fast proliferative cells (Leukemic cells) and possibly a cell cycle arrest (needed to be proved as future perspective) is the mode of action of the extract. To study its effect on targeted cancers, specific in vivo scientific studies and clinical trials should be carried out by further researchers.

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

2020 ◽  
Vol 16 (6) ◽  
pp. 735-749 ◽  
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.

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

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.

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

Molecules ◽  
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.

In vitro chemotherapeutic and antiangiogenic properties of cardenolides from Acokanthera oblongifolia (Hochst.) Codd

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maha M. Soltan ◽  
Howaida I. Abd-Alla ◽  
Amal Z. Hassan ◽  
Atef G. Hanna
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Enzyme Inactivation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Anticancer Properties ◽  
Mechanistic Investigation ◽  
G2m Phase

Abstract Acovenoside A and acobioside A were isolated from Acokanthera oblongifolia. Their anticancer properties were explored regarding, antiproliferative and antiangiogenic activities. The study included screening phase against six cancer cell lines followed by mechanistic investigation against HepG2 cancer cell line. The sulforhodamine-B (SRB) was used to determine their growth inhibitory power. In the other hand, flow cytometry techniques were recorded the cell death type and cell cycle analysis. The clonogenic (colony formation) and wound healing assays, enzyme-linked immunosorbent assay (ELISA) and molecular docking, were performed to evaluate the antiangiogenesis capability. Both compounds were strongly, inhibited four cancer cell lines at GI50 less than 100 nM. The in vitro mechanistic investigation against HepG2 resulted in cell accumulations at G2M phase and induction of apoptosis upon treating cells separately, with 400 nM Acov-A and 200 nM Acob-A. Interestingly, the same concentrations were able to activate caspase-3 by 7.2 and 4.8-fold, respectively. Suppressing the clonogenic capacity of HepG2 cells (20 and 40 nM) and inhibiting the migration of the colon Caco-2 cancer cells were provoke the results of vascular endothelial growth factor receptor2 (VEGFR2) kinase enzyme inactivation. The docked study was highly supportive, to the antiangiogenic approach of both cardenolides. The isolated cardenolides could orchestrate pivotal events in fighting cancer.

scholarly journals Evaluation of cytotoxic profile of hydroalcoholic extract of fruit rinds of Garcinia pedunculata on human embryonic kidney and breast carcinoma cells

2020 ◽  
Vol 9 (2) ◽  
pp. 259
Author(s):  
Sukrant Sharma ◽  
Ravi Mundugaru ◽  
Pradeepa H. Dakappa ◽  
Pundalik R. Naik
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cytotoxic Effect ◽  
Metastatic Breast ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Alcoholic Extract ◽  
Human Embryonic Kidney ◽  
Hek 293

Background: The fruit rinds of Garcinia pedunculata has potential medicinal properties and used in many chronic ailments. It has been demonstrated that cytoprotective effects in various experimental research works. But its cytotoxic effect has not been evaluated. The present study was aimed to screen its relative cytotoxic effect on normal and cancer cell lines.Methods: In the present study, the cytotoxic effect of hydro alcoholic extract of Garcinia pedunculata was evaluated on normal human embryonic kidney (HEK-293) and M.D. Anderson metastatic breast cancer cell lines (MDA-MB 231) using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.Results: Higher dose level of hydro alcoholic extract of Garcinia pedunculata (HAGP) (500 μg/ml) has shown considerable increase (112.503) in the percentage viability of HEK-29 whereas; there is a remarkable decrease in the viable cell population (77.490) in MDA-MB 231.Conclusions: Based on the observed results we could conclude that HAGP has potential cytotoxic effect on the cancer cell line without altering the normal cell growth and proliferation. Thus it has potential to develop as a safer chemotherapeutic agent. Further detailed exploration is required to confirm its therapeutic efficacy in different cancer cell lines.

scholarly journals A Deep Learning Model for Cell Growth Inhibition IC50 Prediction and Its Application for Gastric Cancer Patients

2019 ◽  
Vol 20 (24) ◽  
pp. 6276
Author(s):  
Minjae Joo ◽  
Aron Park ◽  
Kyungdoc Kim ◽  
Won-Joon Son ◽  
Hyo Sug Lee ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Cancer Type ◽  
Molecular Fingerprints ◽  
Drug Responsiveness ◽  
Gastric Cancer Patients ◽  
New Compounds

Heterogeneity in intratumoral cancers leads to discrepancies in drug responsiveness, due to diverse genomics profiles. Thus, prediction of drug responsiveness is critical in precision medicine. So far, in drug responsiveness prediction, drugs’ molecular “fingerprints”, along with mutation statuses, have not been considered. Here, we constructed a 1-dimensional convolution neural network model, DeepIC50, to predict three drug responsiveness classes, based on 27,756 features including mutation statuses and various drug molecular fingerprints. As a result, DeepIC50 showed better cell viability IC50 prediction accuracy in pan-cancer cell lines over two independent cancer cell line datasets. Gastric cancer (GC) is not only one of the lethal cancer types in East Asia, but also a heterogeneous cancer type. Currently approved targeted therapies in GC are only trastuzumab and ramucirumab. Responsive GC patients for the drugs are limited, and more drugs should be developed in GC. Due to the importance of GC, we applied DeepIC50 to a real GC patient dataset. Drug responsiveness prediction in the patient dataset by DeepIC50, when compared to the other models, were comparable to responsiveness observed in GC cell lines. DeepIC50 could possibly accurately predict drug responsiveness, to new compounds, in diverse cancer cell lines, in the drug discovery process.

scholarly journals 8-Hydroxycudraxanthone G Suppresses IL-8 Production in SP-C1 Tongue Cancer Cells

2014 ◽  
Vol 9 (1) ◽  
pp. 1934578X1400900
Author(s):  
Arlette S. Setiawan ◽  
Roosje R. Oewen ◽  
Supriatno ◽  
Willyanti Soewondo ◽  
Sidik ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Therapeutic Intervention ◽  
Tongue Cancer ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Garcinia Mangostana ◽  
Anti Cancer ◽  
Cancer Activity

Production of IL-8 primarily promotes angiogenic responses in cancer cells, which lead to favorable disease progression. Suppressing this production may, therefore, be a significant therapeutic intervention in targeting tumor angiogenesis. This study aimed to evaluate the reduction effects of xanthones in cancer cell lines. Nine known prenylated xanthones (1–9), isolated from the pericarp of Garcinia mangostana Linn (GML), were tested for their ability to suppress IL-8 (interleukin-8) of the SP-C1 (Supri's Clone 1) tongue cancer cell line. Of these compounds, 8-hydroxycudraxanthone-G (4) suppressed IL-8 within 48 hours. This is the first report of 8-hydroxycudraxanthone G suppressing the production of IL-8 (45% at 15.7 μg/mL in 48 hours). These results suggest that the prolonged suppression of IL-8 production by cancer cell lines is concerned in the anti-cancer activity of 8-hydroxycudraxanthone.

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