scholarly journals Identification of Spiro-Fused [3-azabicyclo[3.1.0]hexane]oxindoles as Potential Antitumor Agents: Initial In Vitro Evaluation of Anti-Proliferative Effect and Actin Cytoskeleton Transformation in 3T3 and 3T3-SV40 Fibroblast

2021 ◽  
Vol 22 (15) ◽  
pp. 8264
Author(s):  
Nickolay A. Knyazev ◽  
Stanislav V. Shmakov ◽  
Sofya A. Pechkovskaya ◽  
Alexander S. Filatov ◽  
Alexander V. Stepakov ◽  
...  
Keyword(s):  
Cell Line ◽  
Antitumor Agents ◽  
Tumor Cell Line ◽  
Proliferative Effect ◽  
In Silico Admet ◽  
Murine Fibroblast ◽  
Membrane Protrusions ◽  
Erythroleukemic Cell ◽  
Potential Antitumor

Novel heterocyclic compounds containing 3-spiro[3-azabicyclo[3.1.0]hexane]oxindole framework (4a, 4b and 4c) have been studied as potential antitumor agents. The in silico ADMET (adsorption, distribution, metabolism, excretion and toxicity) analysis was performed on 4a–c compounds with promising antiproliferative activity, previously synthetized and screened against human erythroleukemic cell line K562 tumor cell line. Cytotoxicity of 4a–c against murine fibroblast 3T3 and SV-40 transformed murine fibroblast 3T3-SV40 cell lines were evaluated. The 4a and 4c compounds were cytotoxic against 3T3-SV40 cells in comparison with those of 3T3. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G0/G1 phase. Using confocal microscopy, we found that with 4a and 4c treatment of 3T3 cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 82–97% of cells. The number of 3T3-SV40 cells with stress fibers increased to 7–30% against 2% in control. We discovered that transformed 3T3-SV40 cells after treatment with compounds 4a and 4c significantly reduced the number of cells with filopodium-like membrane protrusions (from 86 % in control cells to 6–18% after treatment), which indirectly suggests a decrease in cell motility. We can conclude that the studied compounds 4a and 4c have a cytostatic effect, which can lead to a decrease in the number of filopodium-like membrane protrusions.

scholarly journals Identification of Spiro-Fused Pyrrolo[3,4-a]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation

2021 ◽  
Vol 22 (21) ◽  
pp. 11997
Author(s):  
Diana. K. Latypova ◽  
Stanislav V. Shmakov ◽  
Sofya A. Pechkovskaya ◽  
Alexander S. Filatov ◽  
Alexander V. Stepakov ◽  
...  
Keyword(s):  
Hela Cell ◽  
Cell Line ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Antitumor Agents ◽  
Hela Cell Lines ◽  
M Phase ◽  
Induced Apoptosis ◽  
Potential Antitumor

A series of heterocyclic compounds containing a spiro-fused pyrrolo[3,4-a]pyrrolizine and tryptanthrin framework have been synthesized and studied as potential antitumor agents. Cytotoxicity of products was screened against human erythroleukemia (K562) and human cervical carcinoma (HeLa) cell lines. Among the screened compounds. 4a, 4b and 5a were active against human erythroleukemia (K562) cell line, while 4a and 5a were active against cervical carcinoma (HeLa) cell line. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G2/M phase and induced apoptosis. Using confocal microscopy, we found that with 4a and 5a treatment of HeLa cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 76–91% of cells. We discovered that HeLa cells after treatment with compounds 4a and 5a significantly reduced the number of cells with filopodium-like membrane protrusions (from 63 % in control cells to 29% after treatment) and a decrease in cell motility.

Design, Synthesis, In vitro and In silico Evaluation of New Hydrazonebased Antitumor Agents as Potent Akt Inhibitors

2020 ◽  
Vol 17 (11) ◽  
pp. 1380-1392
Author(s):  
Emine Merve Güngör ◽  
Mehlika Dilek Altıntop ◽  
Belgin Sever ◽  
Gülşen Akalın Çiftçi
Keyword(s):  
Cell Line ◽  
Anticancer Agents ◽  
In Silico ◽  
Antitumor Agents ◽  
Colorimetric Assay ◽  
Fibroblast Cell ◽  
Lipinski’S Rule ◽  
In Silico Docking ◽  
Embryonic Fibroblast

Background: Akt is overexpressed or activated in a variety of human cancers, including gliomas, lung, breast, ovarian, gastric and pancreatic carcinomas. Akt inhibition leads to the induction of apoptosis and inhibition of tumor growth and therefore extensive efforts have been devoted to the discovery of potent antitumor drugs targeting Akt. Objectives: The objective of this work was to identify potent anticancer agents targeting Akt. Methods: New hydrazone derivatives were synthesized and investigated for their cytotoxic effects on 5RP7 H-ras oncogene transformed rat embryonic fibroblast and L929 mouse embryonic fibroblast cell lines. Besides, the apoptotic effects of the most active compounds on 5RP7 cell line were evaluated using flow cytometry. Their Akt inhibitory effects were also investigated using a colorimetric assay. In silico docking and Absorption, Distribution, Metabolism and Excretion (ADME) studies were also performed using Schrödinger’s Maestro molecular modeling package. Results and Discussion: Compounds 3a, 3d, 3g and 3j were found to be effective on 5RP7 cells (with IC50 values of <0.97, <0.97, 1.13±0.06 and <0.97 μg/mL, respectively) when compared with cisplatin (IC50= 1.87±0.15 μg/mL). It was determined that these four compounds significantly induced apoptosis in 5RP7 cell line. Among them, N'-benzylidene-2-[(4-(4-methoxyphenyl)pyrimidin- 2-yl)thio]acetohydrazide (3g) significantly inhibited Akt (IC50= 0.5±0.08 μg/mL) when compared with GSK690693 (IC50= 0.6±0.05 μg/mL). Docking studies suggested that compound 3g showed good affinity to the active site of Akt (PDB code: 2JDO). According to in silico ADME studies, the compound also complies with Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 3g stands out as a potential orally bioavailable cytotoxic agent and apoptosis inducer targeting Akt.

scholarly journals Identification of spiro-fused pyrrolo[3,4-a]pyrrolizines and tryptanthrines as potential antitumor agents: Synthesis and initial <em>in vitro</em> evaluation

2021 ◽  
Author(s):  
Vitali M. Boitsov ◽  
Diana K. Latypova ◽  
Stanislav V. Shmakov ◽  
Alexander V. Stepakov ◽  
Nickolay A. Knyazev
Keyword(s):  
Antitumor Agents ◽  
Potential Antitumor

scholarly journals Matching anticancer compounds and tumor cell lines by neural networks with ranking loss

2022 ◽  
Vol 4 (1) ◽  
Author(s):  
Paul Prasse ◽  
Pascal Iversen ◽  
Matthias Lienhard ◽  
Kristina Thedinga ◽  
Chris Bauer ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Cancer Cell ◽  
Drug Sensitivity ◽  
Inhibitory Concentration ◽  
Cancer Cell Line ◽  
Tumor Cell Line ◽  
Ranking Problem ◽  
Ranking Loss

ABSTRACT Computational drug sensitivity models have the potential to improve therapeutic outcomes by identifying targeted drug components that are likely to achieve the highest efficacy for a cancer cell line at hand at a therapeutic dose. State of the art drug sensitivity models use regression techniques to predict the inhibitory concentration of a drug for a tumor cell line. This regression objective is not directly aligned with either of these principal goals of drug sensitivity models: We argue that drug sensitivity modeling should be seen as a ranking problem with an optimization criterion that quantifies a drug’s inhibitory capacity for the cancer cell line at hand relative to its toxicity for healthy cells. We derive an extension to the well-established drug sensitivity regression model PaccMann that employs a ranking loss and focuses on the ratio of inhibitory concentration and therapeutic dosage range. We find that the ranking extension significantly enhances the model’s capability to identify the most effective anticancer drugs for unseen tumor cell profiles based in on in-vitro data.

scholarly journals Mechanisms associated with the expression of cisplatin resistance in a human ovarian tumor cell line following exposure to fractionated X-irradiation in vitro

1992 ◽  
Vol 13 (7) ◽  
pp. 1209-1215 ◽  
Author(s):  
Wolfram C.M. Dempke ◽  
Sharon A. Shellard ◽  
Louise K. Hosking ◽  
Anne Marie J. Fichtinger-Schepman ◽  
Bridget T. Hill
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Ovarian Tumor ◽  
Cisplatin Resistance ◽  
Tumor Cell Line ◽  
Ovarian Tumor Cell ◽  
X Irradiation ◽  
Line Following

scholarly journals Periostin induction in tumor cell line explants and inhibition of in vitro cell growth by anti-periostin antibodies

2005 ◽  
Vol 26 (5) ◽  
pp. 908-915 ◽  
Author(s):  
Isabella T. Tai ◽  
Meiru Dai ◽  
Lan Bo Chen
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Cell Line ◽  
Tumor Cell Line

scholarly journals Interleukin 7 induces CD4+ T cell-dependent tumor rejection.

1991 ◽  
Vol 174 (6) ◽  
pp. 1291-1298 ◽  
Author(s):  
H Hock ◽  
M Dorsch ◽  
T Diamantstein ◽  
T Blankenstein
Keyword(s):  
T Cell ◽  
Tumor Cell ◽  
Cell Line ◽  
Tumor Cell Line ◽  
Tumor Rejection ◽  
T Cell Subsets ◽  
Cd4 Cells ◽  
Antitumor Response ◽  
Interleukin 7

The potential of interleukin 7 (IL-7) to induce an antitumor response in vivo was analyzed. Therefore, the IL-7 gene was expressed in the plasmacytoma cell line J558L. Although the growth of IL-7-producing cells was not retarded in vitro, the IL-7-producing cells were completely rejected upon injection into mice. Tumor rejection was observed only in syngeneic but not in nude mice. The tumor-suppressive effect could be abolished by the parallel injection of an anti-IL-7 monoclonal antibody. Immunohistochemical analysis revealed IL-7-dependent infiltration of the tumor tissue by CD4+ and CD8+ T lymphocytes, and also type 3 complement receptor-positive (CR3+) cells, predominantly macrophages. Depletion of T cell subsets in tumor-bearing mice showed the absolute dependence of the antitumor response on CD4+ cells, whereas tumor rejection was unaffected by depletion of CD8+ cells. In addition to CD4+ cells, CR3+ cells were also needed for tumor rejection. The antitumor effect of IL-7 was confirmed by expression of the IL-7 gene in a second tumor cell line of different cellular origin. Together, our results demonstrate that a high local IL-7 concentration at the tumor site obtained by tumor cell-targeted gene transfer leads to tumor rejection involving a cellular mechanism that seems to be different from the ones observed in analogous experiments with other cytokines.

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