?-Lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines

2003 ◽  
Vol 194 (3) ◽  
pp. 325-340 ◽  
Author(s):  
Karyn van de Mark ◽  
James S. Chen ◽  
Kosta Steliou ◽  
Susan P. Perrine ◽  
Douglas V. Faller
Keyword(s):  
Cell Cycle ◽  
Tumor Cell ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Lipoic Acid ◽  
Tumor Cell Lines ◽  
Transformed Cell ◽  
Cycle Arrest ◽  
Dependent Cell ◽  
Transformed Cell Lines

4‐Deoxyraputindole C induces cell death and cell cycle arrest in tumor cell lines

2018 ◽  
Vol 120 (6) ◽  
pp. 9608-9623 ◽  
Author(s):  
Wagner D. Vital ◽  
Heron F. V. Torquato ◽  
Larissa de Oliveira Passos Jesus ◽  
Wagner Alves de Souza Judice ◽  
Maria Fátima das G. F. da Silva ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Tumor Cell ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Tumor Cell Lines ◽  
Cycle Arrest

Tessaric acid derivatives induce G2/M cell cycle arrest in human solid tumor cell lines

2009 ◽  
Vol 17 (17) ◽  
pp. 6251-6256 ◽  
Author(s):  
Leticia G. León ◽  
Osvaldo J. Donadel ◽  
Carlos E. Tonn ◽  
José M. Padrón
Keyword(s):  
Cell Cycle ◽  
Tumor Cell ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Solid Tumor ◽  
Tumor Cell Lines ◽  
M Cell ◽  
Cycle Arrest ◽  
Human Solid Tumor

Chelidonium majus crude extract inhibits migration and induces cell cycle arrest and apoptosis in tumor cell lines

2016 ◽  
Vol 190 ◽  
pp. 362-371 ◽  
Author(s):  
Milena Deljanin ◽  
Mladen Nikolic ◽  
Dejan Baskic ◽  
Danijela Todorovic ◽  
Predrag Djurdjevic ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Cell ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Crude Extract ◽  
Tumor Cell Lines ◽  
Chelidonium Majus ◽  
Cycle Arrest

scholarly journals CRISPR/Cas9 treatment causes extended TP53-dependent cell cycle arrest in human cells

2020 ◽  
Vol 48 (16) ◽  
pp. 9067-9081
Author(s):  
Jonathan M Geisinger ◽  
Tim Stearns
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Target Sequence ◽  
Wild Type ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Dependent Cell ◽  
A Cell

Abstract While the mechanism of CRISPR/Cas9 cleavage is understood, the basis for the large variation in mutant recovery for a given target sequence between cell lines is much less clear. We hypothesized that this variation may be due to differences in how the DNA damage response affects cell cycle progression. We used incorporation of EdU as a marker of cell cycle progression to analyze the response of several human cell lines to CRISPR/Cas9 treatment with a single guide directed to a unique locus. Cell lines with functionally wild-type TP53 exhibited higher levels of cell cycle arrest compared to lines without. Chemical inhibition of TP53 protein combined with TP53 and RB1 transcript silencing alleviated induced arrest in TP53+/+ cells. Using dCas9, we determined this arrest is driven in part by Cas9 binding to DNA. Additionally, wild-type Cas9 induced fewer 53BP1 foci in TP53+/+ cells compared to TP53−/− cells and DD-Cas9, suggesting that differences in break sensing are responsible for cell cycle arrest variation. We conclude that CRISPR/Cas9 treatment induces a cell cycle arrest dependent on functional TP53 as well as Cas9 DNA binding and cleavage. Our findings suggest that transient inhibition of TP53 may increase genome editing recovery in primary and TP53+/+ cell lines.

scholarly journals CRISPR/Cas9 Treatment Causes Extended TP53-Dependent Cell Cycle Arrest In Human Cells

2019 ◽  
Author(s):  
Jonathan M. Geisinger ◽  
Tim Stearns
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Target Sequence ◽  
Wild Type ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Dependent Cell ◽  
A Cell

ABSTRACTWhile the mechanism of CRISPR/Cas9 cleavage is understood, the large variation in mutant recovery for a given target sequence between cell lines is much less clear. We hypothesized that this variation may be due to differences in how the DNA damage response affects cell cycle progression. We used incorporation of EdU as a marker of cell cycle progression to analyze the response of several human cell lines to CRISPR/Cas9 treatment with a single guide directed to a unique locus. Cell lines with functionally wild-type TP53 exhibited higher levels of cell cycle arrest compared to lines without. Chemical inhibition of TP53 protein combined with TP53 and RB1 transcript silencing alleviated induced arrest in TP53+/+ cells. This arrest is driven in part by Cas9 binding to DNA. Additionally, wild-type Cas9 induced fewer 53BP1 foci in TP53+/+ cells compared to TP53−/− cells, suggesting that differences in break sensing are responsible for cell cycle arrest variation. We conclude that CRISPR/Cas9 treatment induces a cell cycle arrest dependent on functional TP53 as well as Cas9 DNA binding and cleavage. Our findings suggest that transient inhibition of TP53 may increase genome editing efficiency in primary and TP53+/+ cell lines.

scholarly journals DDRE-03. IDH1-MUTANT GBM CELLS ARE HIGHLY SENSITIVE TO COMBINATION OF KDM6A/B AND HDAC INHIBITORS

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. i6-i7
Author(s):  
Alişan Kayabölen ◽  
Gizem Nur Sahin ◽  
Fidan Seker ◽  
Ahmet Cingöz ◽  
Bekir Isik ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Mutant Cell ◽  
Glioma Cells ◽  
Epigenetic Therapy ◽  
Low Grade ◽  
Orthotopic Model ◽  
Cycle Arrest ◽  
Mutant Cells

Abstract Mutations in IDH1 and IDH2 genes are common in low grade gliomas and secondary GBM and are known to cause a distinct epigenetic landscape in these tumors. To interrogate the epigenetic vulnerabilities of IDH-mutant gliomas, we performed a chemical screen with inhibitors of chromatin modifiers and identified 5-azacytidine, Chaetocin, GSK-J4 and Belinostat as potent agents against primary IDH1-mutant cell lines. Testing the combinatorial efficacy of these agents, we demonstrated GSK-J4 and Belinostat combination as a very effective treatment for the IDH1-mutant glioma cells. Engineering established cell lines to ectopically express IDH1R132H, we showed that IDH1R132H cells adopted a different transcriptome with changes in stress-related pathways that were reversible with the mutant IDH1 inhibitor, GSK864. The combination of GSK-J4 and Belinostat was highly effective on IDH1R132H cells, but not on wt glioma cells or nonmalignant fibroblasts and astrocytes. The cell death induced by GSK-J4 and Belinostat combination involved the induction of cell cycle arrest and apoptosis. RNA sequencing analyses revealed activation of inflammatory and unfolded protein response pathways in IDH1-mutant cells upon treatment with GSK-J4 and Belinostat conferring increased stress to glioma cells. Specifically, GSK-J4 induced ATF4-mediated integrated stress response and Belinostat induced cell cycle arrest in primary IDH1-mutant glioma cells; which were accompanied by DDIT3/CHOP-dependent upregulation of apoptosis. Moreover, to dissect out the responsible target histone demethylase, we undertook genetic approach and demonstrated that CRISPR/Cas9 mediated ablation of both KDM6A and KDM6B genes phenocopied the effects of GSK-J4 in IDH1-mutant cells. Finally, GSK-J4 and Belinostat combination significantly decreased tumor growth and increased survival in an orthotopic model in mice. Together, these results suggest a potential combination epigenetic therapy against IDH1-mutant gliomas.

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