scholarly journals Protein Kinase CK2 Is a Central Regulator of Topoisomerase I Hyperphosphorylation and Camptothecin Sensitivity in Cancer Cell Lines

Biochemistry ◽  
2011 ◽  
Vol 50 (5) ◽  
pp. 704-714 ◽  
Author(s):  
Keya Bandyopadhyay ◽  
Ruth A. Gjerset
Keyword(s):  
Protein Kinase ◽  
Cell Lines ◽  
Cancer Cell ◽  
Topoisomerase I ◽  
Protein Kinase Ck2 ◽  
Cancer Cell Lines ◽  
Kinase Ck2

scholarly journals 5,6-diiodo-1H-benzotriazole: new TBBt analogue that minutely affects mitochondrial activity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Paprocki ◽  
Maria Winiewska-Szajewska ◽  
Elżbieta Speina ◽  
Róża Kucharczyk ◽  
Jarosław Poznański
Keyword(s):  
Protein Kinase ◽  
Cell Lines ◽  
Cancer Cell ◽  
Protein Kinase Ck2 ◽  
Cancer Cell Lines ◽  
Competitive Inhibitor ◽  
Attractive Alternative ◽  
Mitochondrial Activity ◽  
Mitochondrial Inner Membrane ◽  
Kinase Ck2

Abstract4,5,6,7-Tetrabromo-1H-benzotriazole is widely used as the reference ATP-competitive inhibitor of protein kinase CK2. Herein, we study its new analogs: 5,6-diiodo- and 5,6-diiodo-4,7-dibromo-1H-benzotriazole. We used biophysical (MST, ITC) and biochemical (enzymatic assay) methods to describe the interactions of halogenated benzotriazoles with the catalytic subunit of human protein kinase CK2 (hCK2α). To trace the biological activity, we measured their cytotoxicity against four reference cancer cell lines and the effect on the mitochondrial inner membrane potential. The results obtained lead to the conclusion that iodinated compounds are an attractive alternative to brominated ones. One of them retains the cytotoxicity against selected cancer cell lines of the reference TBBt with a smaller side effect on mitochondrial activity. Both iodinated compounds are candidate leaders in the further development of CK2 inhibitors.

scholarly journals CX-4945 Induces Methuosis in Cholangiocarcinoma Cell Lines by a CK2-Independent Mechanism

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 283 ◽  
Author(s):  
Jomnarong Lertsuwan ◽  
Kornkamon Lertsuwan ◽  
Anyaporn Sawasdichai ◽  
Nathapol Tasnawijitwong ◽  
Ka Lee ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Protein Kinase Ck2 ◽  
Extracellular Fluid ◽  
Multiple Cancer ◽  
Cholangiocarcinoma Cell ◽  
Kinase Ck2

Cholangiocarcinoma is a disease with a poor prognosis and increasing incidence and hence there is a pressing unmet clinical need for new adjuvant treatments. Protein kinase CK2 (previously casein kinase II) is a ubiquitously expressed protein kinase that is up-regulated in multiple cancer cell types. The inhibition of CK2 activity using CX-4945 (Silmitasertib) has been proposed as a novel treatment in multiple disease settings including cholangiocarcinoma. Here, we show that CX-4945 inhibited the proliferation of cholangiocarcinoma cell lines in vitro. Moreover, CX-4945 treatment induced the formation of cytosolic vacuoles in cholangiocarcinoma cell lines and other cancer cell lines. The vacuoles contained extracellular fluid and had neutral pH, features characteristic of methuosis. In contrast, simultaneous knockdown of both the α and α′ catalytic subunits of protein kinase CK2 using small interfering RNA (siRNA) had little or no effect on the proliferation of cholangiocarcinoma cell lines and failed to induce the vacuole formation. Surprisingly, low doses of CX-4945 increased the invasive properties of cholangiocarcinoma cells due to an upregulation of matrix metallopeptidase 7 (MMP-7), while the knockdown of CK2 inhibited cell invasion. Our data suggest that CX-4945 inhibits cell proliferation and induces cell death via CK2-independent pathways. Moreover, the increase in cell invasion brought about by CX-4945 treatment suggests that this drug might increase tumor invasion in clinical settings.

scholarly journals Nanog expression is negatively regulated by protein kinase C activities in human cancer cell lines

2013 ◽  
Vol 34 (7) ◽  
pp. 1497-1509 ◽  
Author(s):  
Wing-Keung Chu ◽  
Pei-Min Dai ◽  
Hsin-Lun Li ◽  
Chia-Chu Pao ◽  
Jan-Kan Chen
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Nanog Expression ◽  
Kinase C

scholarly journals Proteomic Analysis of Nuclei Isolated from Cancer Cell Lines Treated with Indenoisoquinoline NSC 724998, a Novel Topoisomerase I Inhibitor

2010 ◽  
Vol 9 (8) ◽  
pp. 4016-4027 ◽  
Author(s):  
Bingnan Han ◽  
Luke H. Stockwin ◽  
Chad Hancock ◽  
Sherry X. Yu ◽  
Melinda G. Hollingshead ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Proteomic Analysis ◽  
Topoisomerase I ◽  
Cancer Cell Lines ◽  
Topoisomerase I Inhibitor

High-Throughput RNA Interference Screening Identifies Synthetic Lethality Between Oncogenic KRAS Dependency and Suppression of STK33

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3806-3806
Author(s):  
Claudia Scholl ◽  
Stefan Frohling ◽  
Ian F. Dunn ◽  
David A. Barbie ◽  
Anna C. Schinzel ◽  
...  
Keyword(s):  
Rna Interference ◽  
Protein Kinase ◽  
Cell Viability ◽  
Cell Lines ◽  
Cancer Cell ◽  
High Throughput ◽  
Synthetic Lethality ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Dependent Manner

Abstract Activating RAS mutations are among the most common pathogenetic events in a broad spectrum of hematologic malignancies and epithelial tumors. However, oncogenic RAS has thus far not proven to be a tractable target for therapeutic intervention. An alternative to direct targeting of known oncogenes is to perform “synthetic lethality” screens to identify genes that are selectively required for cell viability in the context of specific cancer-causing mutations. Using this approach, we have discovered a synthetic lethal interaction between mutant KRAS, the most frequently mutated oncogene in human cancer, and inactivation of the gene encoding the STK33 serine/threonine protein kinase. To identify genes that are essential for cell viability in the context of mutant KRAS, we performed high-throughput loss-of-function RNA interference (RNAi) screens in eight human cancer cell lines (mutant KRAS, n=4; wildtype KRAS, n=4), representing seven different tumor types (acute myeloid leukemia, multiple myeloma, colon cancer, breast cancer, ovarian cancer, prostate cancer, glioblastoma), as well as normal human fibroblasts and mammary epithelial cells. We screened each cell line with a subset of the short hairpin RNA (shRNA) library developed by the RNAi Consortium (http://www.broad.mit.edu/genome_bio/trc/rnai.html) that consists of 5,024 individual shRNA constructs targeting 1,011 human genes, including the majority of known and putative protein kinase and phosphatase genes and a selection of known cancer-related genes. In these cell lines, suppression of STK33 preferentially inhibited the viability and proliferation of cells that were dependent on mutant KRAS. The differential requirement for STK33 based on oncogenic KRAS dependency was confirmed in 16 additional cell lines using in vitro transformation assays and human tumor xenograft models. Biochemical analyses support the hypothesis that STK33 promotes cell growth and survival in a kinase activity-dependent manner by regulating the activity of S6K1 as well as BAD-induced apoptosis selectively in mutant KRAS-dependent cells. Notably, molecular genetic characterization of cancer cell lines and analysis of patient-derived genomic data sets indicate that STK33 is not frequently mutated or overexpressed in human tumors. These observations identify STK33 as a potential target for the treatment of mutant KRAS-driven cancers that may have a broad therapeutic index in normal versus malignant cells, and illustrate the potential of RNAi for discovering critical functional dependencies created by oncogenic mutations that cannot be identified using other genomic technologies.

scholarly journals Proteomic Analysis of Nuclei Isolated from Cancer Cell Lines Treated with Indenoisoquinoline NSC 724998, a Novel Topoisomerase I Inhibitor

2011 ◽  
Vol 10 (4) ◽  
pp. 2128-2128
Author(s):  
Bingnan Han ◽  
Luke H. Stockwin ◽  
Chad Hancock ◽  
Sherry X. Yu ◽  
Melinda G. Hollingshead ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Proteomic Analysis ◽  
Topoisomerase I ◽  
Cancer Cell Lines ◽  
Topoisomerase I Inhibitor

scholarly journals Targeting protein kinase CK2 suppresses bladder cancer cell survival via the glucose metabolic pathway

Oncotarget ◽  
2016 ◽  
Vol 7 (52) ◽  
pp. 87361-87372 ◽  
Author(s):  
Xiaolei Zhang ◽  
Xiao Yang ◽  
Chengdi Yang ◽  
Peng Li ◽  
Wenbo Yuan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Protein Kinase ◽  
Cell Survival ◽  
Cancer Cell ◽  
Metabolic Pathway ◽  
Protein Kinase Ck2 ◽  
Bladder Cancer Cell ◽  
Cancer Cell Survival ◽  
Kinase Ck2

scholarly journals The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

2018 ◽  
Vol 19 (10) ◽  
pp. 2861 ◽  
Author(s):  
Dimakatso Senthebane ◽  
Tina Jonker ◽  
Arielle Rowe ◽  
Nicholas Thomford ◽  
Daniella Munro ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Esophageal Cancer ◽  
Protein Kinase ◽  
Cell Lines ◽  
Cancer Cell ◽  
Colony Formation ◽  
Cancer Cell Lines ◽  
Chemotherapeutic Drugs ◽  
Ecm Proteins ◽  
Esophageal Cancer Cell

Background: The functional interplay between tumor cells and their adjacent stroma has been suggested to play crucial roles in the initiation and progression of tumors and the effectiveness of chemotherapy. The extracellular matrix (ECM), a complex network of extracellular proteins, provides both physical and chemicals cues necessary for cell proliferation, survival, and migration. Understanding how ECM composition and biomechanical properties affect cancer progression and response to chemotherapeutic drugs is vital to the development of targeted treatments. Methods: 3D cell-derived-ECMs and esophageal cancer cell lines were used as a model to investigate the effect of ECM proteins on esophageal cancer cell lines response to chemotherapeutics. Immunohistochemical and qRT-PCR evaluation of ECM proteins and integrin gene expression was done on clinical esophageal squamous cell carcinoma biopsies. Esophageal cancer cell lines (WHCO1, WHCO5, WHCO6, KYSE180, KYSE 450 and KYSE 520) were cultured on decellularised ECMs (fibroblasts-derived ECM; cancer cell-derived ECM; combinatorial-ECM) and treated with 0.1% Dimethyl sulfoxide (DMSO), 4.2 µM cisplatin, 3.5 µM 5-fluorouracil and 2.5 µM epirubicin for 24 h. Cell proliferation, cell cycle progression, colony formation, apoptosis, migration and activation of signaling pathways were used as our study endpoints. Results: The expression of collagens, fibronectin and laminins was significantly increased in esophageal squamous cell carcinomas (ESCC) tumor samples compared to the corresponding normal tissue. Decellularised ECMs abrogated the effect of drugs on cancer cell cycling, proliferation and reduced drug induced apoptosis by 20–60% that of those plated on plastic. The mitogen-activated protein kinase-extracellular signal-regulated kinase (MEK-ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K/Akt) signaling pathways were upregulated in the presence of the ECMs. Furthermore, our data show that concomitant addition of chemotherapeutic drugs and the use of collagen- and fibronectin-deficient ECMs through siRNA inhibition synergistically increased cancer cell sensitivity to drugs by 30–50%, and reduced colony formation and cancer cell migration. Conclusion: Our study shows that ECM proteins play a key role in the response of cancer cells to chemotherapy and suggest that targeting ECM proteins can be an effective therapeutic strategy against chemoresistant tumors.

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