The checkpoint 1 kinase inhibitor LY2603618 induces cell cycle arrest, DNA damage response and autophagy in cancer cells

APOPTOSIS ◽  
2014 ◽  
Vol 19 (9) ◽  
pp. 1389-1398 ◽  
Author(s):  
Feng-Ze Wang ◽  
Hong-rong Fei ◽  
Ying-Jie Cui ◽  
Ying-Kun Sun ◽  
Zhao-Mei Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Dna Damage Response ◽  
Kinase Inhibitor ◽  
Cycle Arrest ◽  
Damage Response

RO3280: A Novel PLK1 Inhibitor, Suppressed the Proliferation of MCF-7 Breast Cancer Cells Through the Induction of Cell Cycle Arrest at G2/M Point

2019 ◽  
Vol 19 (15) ◽  
pp. 1846-1854 ◽  
Author(s):  
Mustafa Ergul ◽  
Filiz Bakar-Ates
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Dna Damage Response ◽  
Breast Cancer Cells ◽  
Cycle Arrest ◽  
Damage Response ◽  
Mcf 7

Background: As a member of serine/threonine-protein kinase, Polo‐like kinase 1 (PLK1) plays crucial roles during mitosis and also contributes to DNA damage response and repair. PLK1 is aberrantly expressed in many types of tumor cells and increased levels of PLK1 is closely related to tumorigenesis and poor clinical outcomes. Therefore, PLK1 is accepted as one of the potential targets for the discovery of novel anticancer agents. The objective of this study was to assess the cytotoxic effects of a novel PLK1 inhibitor, RO3280, against MCF-7, human breast cancer cells; HepG2, human hepatocellular carcinoma cells; and PC3, human prostate cancer cells, as well as non-cancerous L929 fibroblast cells. Methods: Antiproliferative activity of RO3280 was examined using the XTT assay. Flow cytometry assay was performed to evaluate cell cycle distribution, apoptosis, multicaspase activity, mitochondrial membrane potential, and DNA damage response. We also examined apoptosis with fluorescence imaging studies. Results: According to the results of XTT assay, although RO3280 displayed potent cytotoxicity in all treated cancer cells, the most sensitive cell line was identified as MCF-7 cells that were selected for further studies. The compound induced a cell cycle arrest in MCF-7 cells at G2/M phase and significantly induced apoptosis, multicaspase activity, DNA damage response, and decreased mitochondrial membrane potential of MCF-7 cells. Conclusion: Overall, RO3280 induces anticancer effects promoted mainly by DNA damage, cell cycle arrest, and apoptosis in breast cancer cells. Further studies are needed to assess its usability as an anticancer agent with specific cancer types.

scholarly journals RUNX Family Participates in the Regulation of p53-Dependent DNA Damage Response

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Toshinori Ozaki ◽  
Akira Nakagawara ◽  
Hiroki Nagase
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Dna Damage Response ◽  
Apoptotic Cell ◽  
Genetic Alterations ◽  
Apoptotic Cell Death ◽  
Cycle Arrest ◽  
Damage Response

A proper DNA damage response (DDR), which monitors and maintains the genomic integrity, has been considered to be a critical barrier against genetic alterations to prevent tumor initiation and progression. The representative tumor suppressor p53 plays an important role in the regulation of DNA damage response. When cells receive DNA damage, p53 is quickly activated and induces cell cycle arrest and/or apoptotic cell death through transactivating its target genes implicated in the promotion of cell cycle arrest and/or apoptotic cell death such asp21WAF1,BAX, andPUMA. Accumulating evidence strongly suggests that DNA damage-mediated activation as well as induction of p53 is regulated by posttranslational modifications and also by protein-protein interaction. Loss of p53 activity confers growth advantage and ensures survival in cancer cells by inhibiting apoptotic response required for tumor suppression. RUNX family, which is composed of RUNX1, RUNX2, and RUNX3, is a sequence-specific transcription factor and is closely involved in a variety of cellular processes including development, differentiation, and/or tumorigenesis. In this review, we describe a background of p53 and a functional collaboration between p53 and RUNX family in response to DNA damage.

scholarly journals Inhibition of p53 improves CRISPR/Cas - mediated precision genome editing

2017 ◽  
Author(s):  
Emma Haapaniemi ◽  
Sandeep Botla ◽  
Jenna Persson ◽  
Bernhard Schmierer ◽  
Jussi Taipale
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Homologous Recombination ◽  
Cell Cycle Arrest ◽  
Genome Editing ◽  
Dna Damage Response ◽  
Normal Cells ◽  
Cycle Arrest ◽  
Damage Response

AbstractWe report here that genome editing by CRISPR/Cas9 induces a p53-mediated DNA damage response and cell cycle arrest. Transient inhibition of p53 prevents this response, and increases the rate of homologous recombination more than five-fold. This provides a way to improve precision genome editing of normal cells, but warrants caution in using CRISPR for human therapies until the mechanism of the activation of p53 is elucidated.

scholarly journals The Oxygen-Rich Postnatal Environment Induces Cardiomyocyte Cell-Cycle Arrest through DNA Damage Response

Cell ◽  
2014 ◽  
Vol 157 (3) ◽  
pp. 565-579 ◽  
Author(s):  
Bao N. Puente ◽  
Wataru Kimura ◽  
Shalini A. Muralidhar ◽  
Jesung Moon ◽  
James F. Amatruda ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Dna Damage Response ◽  
Cycle Arrest ◽  
Damage Response ◽  
Postnatal Environment

scholarly journals Human Parvovirus B19 DNA Replication Induces a DNA Damage Response That Is Dispensable for Cell Cycle Arrest at Phase G2/M

2012 ◽  
Vol 86 (19) ◽  
pp. 10748-10758 ◽  
Author(s):  
S. Lou ◽  
Y. Luo ◽  
F. Cheng ◽  
Q. Huang ◽  
W. Shen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Replication ◽  
Cell Cycle Arrest ◽  
Dna Damage Response ◽  
Parvovirus B19 ◽  
Human Parvovirus B19 ◽  
Cycle Arrest ◽  
Damage Response

scholarly journals ATM: Main Features, Signaling Pathways, and Its Diverse Roles in DNA Damage Response, Tumor Suppression, and Cancer Development

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 845
Author(s):  
Liem Minh Phan ◽  
Abdol-Hossein Rezaeian
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Signaling Pathways ◽  
Dna Damage Response ◽  
Cancer Development ◽  
Cellular Processes ◽  
Cycle Arrest ◽  
Damage Response ◽  
Cancer Cell Survival

ATM is among of the most critical initiators and coordinators of the DNA-damage response. ATM canonical and non-canonical signaling pathways involve hundreds of downstream targets that control many important cellular processes such as DNA damage repair, apoptosis, cell cycle arrest, metabolism, proliferation, oxidative sensing, among others. Of note, ATM is often considered a major tumor suppressor because of its ability to induce apoptosis and cell cycle arrest. However, in some advanced stage tumor cells, ATM signaling is increased and confers remarkable advantages for cancer cell survival, resistance to radiation and chemotherapy, biosynthesis, proliferation, and metastasis. This review focuses on addressing major characteristics, signaling pathways and especially the diverse roles of ATM in cellular homeostasis and cancer development.

scholarly journals What Lies in between Telomere and Organismal Ageing: Comparison between Replicative Senescence and Stress-Induced Premature Senescence

2021 ◽  
Vol 245 ◽  
pp. 03051
Author(s):  
Hanyi Jia
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Dna Damage Response ◽  
Replicative Senescence ◽  
Premature Senescence ◽  
Cycle Arrest ◽  
Damage Response ◽  
Permanent Cell ◽  
Stress Induced Premature Senescence

A mitotic cell that rests in permanent cell cycle arrest without the ability to divide is considered as a senescent cell. Cellular senescence is essential to limit the function of cells with heavy DNA damages. The lack of senescence is in favour of tumorigenesis, whereas the accumulation of senescent cells in tissues is likely to induce ageing and age-related pathologies on the organismal level. Understanding of cellular senescence is thus critical to both cancer and ageing studies. Senescence, essentially permanent cell cycle arrest, is one of the results of DNA damage response, such as the ataxia telangiectasia mutated and the ataxia telangiectasia and Rad3-related signaling pathways. In other cases, mild DNA damages can usually be repaired after DNA damage response, while the cells with heavy damages on DNA end in apoptosis. The damage to the special structure of telomere, however, prone to result in permanent cell cycle arrest after activation of DNA damage response. In fact, a few previous pieces of research on ageing have largely focused on telomere and considered it a primary contributor to different types of senescence. For instance, its reduction in length after each replication turns on a timer for replicative senescence, and its tandem repeats specific to binding proteins makes it susceptible to DNA damage from oxidative stress, and thus stress-induced premature senescence. In most of the senescent cells, the accumulation of biomarkers is found around the telomere which has either its tail structure disassembled or damage foci exposed on the tandem repeats. In this review, among several types of senescence, I will investigate two of the most common and widely discussed types in eukaryotic cells -replicative senescence and stress-induced premature senescence - in terms of their mechanism, relationship with telomere, and implication to organismal ageing.

scholarly journals Cytokinesis failure in RhoA-deficient mouse erythroblasts involves actomyosin and midbody dysregulation and triggers p53 activation

Blood ◽  
2015 ◽  
Vol 126 (12) ◽  
pp. 1473-1482 ◽  
Author(s):  
Diamantis G. Konstantinidis ◽  
Katie M. Giger ◽  
Mary Risinger ◽  
Suvarnamala Pushkaran ◽  
Ping Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Dna Damage Response ◽  
Deficient Mouse ◽  
Cycle Arrest ◽  
Rhoa Gtpase ◽  
Key Points ◽  
Damage Response ◽  
P53 Activation

Key Points RhoA GTPase activates pMRLC and localizes to the site of midbody formation to regulate erythroblast cytokinesis. Cytokinesis failure in erythroblasts caused by RhoA deficiency triggers p53-mediated DNA-damage response, cell-cycle arrest, and apoptosis.

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