Pharmacological profiling of disulfiram using human tumor cell lines and human tumor cells from patients

2007 ◽  
Vol 73 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Malin Wickström ◽  
Katarina Danielsson ◽  
Linda Rickardson ◽  
Joachim Gullbo ◽  
Peter Nygren ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cells ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

scholarly journals Unraveling the functional relevance of the Ubiquitin-specific peptidase 22 for necroptotic cell death

2021 ◽  
Author(s):  
◽  
Jens Rödig
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Cell Death Signaling

Ubiquitination is regarded as one of the key post-translational modifications in nearly all biological processes, endowed with numerous layers of complexity. Deubiquitinating enzymes (DUBs) dynamically counterbalance ubiquitination events by deconjugating ubiquitin signals from substrates. Dysregulation of the ubiquitin code and its negative regulators drive various pathologies, such as neurological disorders and cancer. The DUB ubiquitin-specific peptidase 22 (USP22) is well-known for its essential role in the human Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, mediating the removal of monoubiquitination events from Histone 2A and 2B (H2A and -B), thereby regulating gene transcription. In cancer, USP22 was initially described as a part of an 11-gene expression signature profile, predicting tumor metastasis, reoccurrence and death after therapy in a wide range of tumor cells. However, novel roles for USP22 have emerged recently, accrediting USP22 essential roles in regulating tumor development as well as apoptotic cell death signaling. One of the hallmarks of cancer is the evasion of cell death, especially apoptosis, a form of programmed cell death (PCD). Necroptosis, a regulated form of necrosis, is regarded as an attractive therapeutic strategy to overcome apoptosis-resistance in tumor cells, although a profound understanding of the exact signaling cascade still remains elusive. Nevertheless, several ubiquitination and deubiquitination events are described in fine-tuning necroptotic signaling. In this study, we describe a novel role for USP22 in regulating necroptotic cell death signaling in human tumor cell lines. USP22 depletion significantly delayed TNFa/Smac mimetic/zVAD.fmk (TBZ)-induced necroptosis, without affecting TNFa-induced nuclear factor-kappa B (NF-KB) signaling or TNFa-mediated extrinsic apoptosis. Intriguingly, re-expression of USP22 wildtype in the USP22 knockout background could re-sensitize HT-29 cells to TBZ-induced necroptosis, whereas re-constitution with the catalytic inactive mutant USP22 Cys185Ser did not rescue susceptibility to TBZ-induced necroptosis, confirming the USP22 DUB-function a pivotal role in regulating necroptotic cell death. USP22 depletion facilitated ubiquitination and unexpectedly also phosphorylation of Receptor-interacting protein kinase 3 (RIPK3) during necroptosis induction, as shown by Tandem Ubiquitin Binding Entities (TUBE) pulldowns and in vivo (de)ubiquitination immunoprecipitations. To substantiate our findings, we performed mass-spectrometric ubiquitin remnant profiling and identified the three novel USP22-regulated RIPK3 ubiquitination sites Lysine (K) 42, K351 and K518 upon TBZ-induced necroptosis. Further assessment of these ubiquitination sites unraveled, that mutation of K518 in RIPK3 reduced necroptosis-associated RIPK3 ubiquitination and additionally affected RIPK3 phosphorylation upon necroptosis induction. At the same time, genetic knock-in of RIPK3 K518R sensitizes tumor cells to TNFa-induced necroptotic cell death and amplified necrosome formation. In summary we identified USP22 as a new regulator of TBZ-induced necroptosis in various human tumor cell lines and further unraveled the distinctive role of DUBs and (de)ubiquitination events in controlling programmed cell death signaling.

Differential Increases in Glutathione S-Transferase Activities in a Range of Multidrug-Resistant Human Tumor Cell Lines

1989 ◽  
Vol 1 (6) ◽  
pp. 359-365 ◽  
Author(s):  
Richard D. H. Whelan ◽  
Louise K. Hosking ◽  
Alan J. Townsend ◽  
Kenneth H. Cowan ◽  
Bridget T. Hill
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Multidrug Resistant ◽  
Tumor Cell Lines ◽  
Glutathione S Transferase ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

2020 ◽  
Vol 17 (4) ◽  
pp. 512-517
Author(s):  
Ognyan Ivanov Petrov ◽  
Yordanka Borisova Ivanova ◽  
Mariana Stefanova Gerova ◽  
Georgi Tsvetanov Momekov
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Biological Activities ◽  
Human Tumor ◽  
Mannich Bases ◽  
In Vitro Cytotoxicity ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments. Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined. Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable. Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

scholarly journals Anticancer activity of pyrimidodiazepines based on 2-chloro-4-anilinoquinazoline: synthesis, DNA binding and molecular docking

RSC Advances ◽  
2021 ◽  
Vol 11 (38) ◽  
pp. 23310-23329
Author(s):  
Viviana Cuartas ◽  
Alberto Aragón-Muriel ◽  
Yamil Liscano ◽  
Dorian Polo-Cerón ◽  
Maria del Pilar Crespo-Ortiz ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Dna Binding ◽  
Tumor Cell ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

A new series of quinazoline-based chalcones and pyrimidodiazepines were tested against 60 human tumor cell lines.

scholarly journals Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 92
Author(s):  
Bashir Lawal ◽  
Yen-Lin Liu ◽  
Ntlotlang Mokgautsi ◽  
Harshita Khedkar ◽  
Maryam Rachmawati Sumitra ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Tumor ◽  
Cancer Cell Lines ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Anti Cancer

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies

1993 ◽  
Vol 37 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Gail D. Lewis ◽  
Irene Figari ◽  
Brian Fendly ◽  
Wai Lee Wong ◽  
Paul Carter ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Differential Responses

Preclinical Evaluation of ZD1839 Alone or in Combination with Oxaliplatin in a Panel of Human Tumor Cell Lines – Implications for Clinical Use

2005 ◽  
Vol 28 (10) ◽  
pp. 482-488 ◽  
Author(s):  
Wieland Voigt ◽  
Volker Pickan ◽  
Claudio Pfeiffer ◽  
Thomas Mueller ◽  
Heike Simon ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Clinical Use ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines ◽  
Preclinical Evaluation

Synthesis and Characterization of New Palladium(II) Complexes with Ligands Derived from Furan-2-carbaldehyde and Benzaldehyde Thiosemicarbazone and their in vitro Cytotoxic Activities against Various Human Tumor Cell Lines

2010 ◽  
Vol 65 (10) ◽  
pp. 1271-1278 ◽  
Author(s):  
Wilfredo Hernández ◽  
Juan Paz ◽  
Fernando Carrasco ◽  
Abraham Vaisberg ◽  
Jorge Manzur ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Human Tumor ◽  
Myelogenous Leukemia ◽  
Cytotoxic Activities ◽  
Spectroscopic Techniques ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor Cell Lines

With the ligands 4-phenyl-1-(furan-2-carbaldehyde)thiosemicarbazone, HTSC1, (1), 4-phenyl-1- (5´-phenyl-furan-2-carbaldehyde)thiosemicarbazone, HTSC2 (2), o-methoxy-benzaldehydethiosemicarbazone, HTSC3 (3), and o-cyano-benzaldehydethiosemicarbazone, HTSC4 (4), the corresponding palladium(II) complexes, Pd(TSC1)2 (5), Pd(TSC2)2 (6), Pd(TSC3)2 (7), and Pd(TSC4)2 (8) were synthesized and characterized by elemental analysis and spectroscopic techniques. The crystal structure of Pd(TSC3)2 (7) was determined by single-crystal X-ray diffraction. Complex 7 shows a squareplanar geometry, where two deprotonated ligands are coordinated to the PdII center through the nitrogen and sulfur atoms in a trans arrangement. In vitro antitumor studies against different human tumor cell lines have revealed that the palladium(II) complexes 5- 8 are more cytotoxic (IC50 values in the range of 0.21 - 3.79 μM) than their corresponding ligands (1 - 4) (> 60 μM). These results indicate that the antiproliferative activity is enhanced when thiosemicarbazone ligands are coordinated to the metal. Among the studied palladium(II) complexes, 8 exhibits high antitumor activity on K562 chronic myelogenous leukemia cells with a low value of the inhibitory concentration (IC50 = 0.21 μM).

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