scholarly journals Senescence-Associated Secretory Phenotype as a Hinge Between Cardiovascular Diseases and Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Priyanka Banerjee ◽  
Sivareddy Kotla ◽  
Loka Reddy Velatooru ◽  
Rei J. Abe ◽  
Elizabeth A. Davis ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cardiovascular Diseases ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Replicative Senescence ◽  
Cancer Treatments ◽  
Cycle Arrest ◽  
Secretory Phenotype ◽  
Mediate Cell

Overlapping risks for cancer and cardiovascular diseases (CVD), the two leading causes of mortality worldwide, suggest a shared biology between these diseases. The role of senescence in the development of cancer and CVD has been established. However, its role as the intersection between these diseases remains unclear. Senescence was originally characterized by an irreversible cell cycle arrest after a high number of divisions, namely replicative senescence (RS). However, it is becoming clear that senescence can also be instigated by cellular stress, so-called stress-induced premature senescence (SIPS). Telomere shortening is a hallmark of RS. The contribution of telomere DNA damage and subsequent DNA damage response/repair to SIPS has also been suggested. Although cellular senescence can mediate cell cycle arrest, senescent cells can also remain metabolically active and secrete cytokines, chemokines, growth factors, and reactive oxygen species (ROS), so-called senescence-associated secretory phenotype (SASP). The involvement of SASP in both cancer and CVD has been established. In patients with cancer or CVD, SASP is induced by various stressors including cancer treatments, pro-inflammatory cytokines, and ROS. Therefore, SASP can be the intersection between cancer and CVD. Importantly, the conventional concept of senescence as the mediator of cell cycle arrest has been challenged, as it was recently reported that chemotherapy-induced senescence can reprogram senescent cancer cells to acquire “stemness” (SAS: senescence-associated stemness). SAS allows senescent cancer cells to escape cell cycle arrest with strongly enhanced clonogenic growth capacity. SAS supports senescent cells to promote both cancer and CVD, particularly in highly stressful conditions such as cancer treatments, myocardial infarction, and heart failure. As therapeutic advances have increased overlapping risk factors for cancer and CVD, to further understand their interaction may provide better prevention, earlier detection, and safer treatment. Thus, it is critical to study the mechanisms by which these senescence pathways (SAS/SASP) are induced and regulated in both cancer and CVD.

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 LFZ-4-46, a tetrahydroisoquinoline derivative, induces apoptosis and cell cycle arrest via induction of DNA damage and activation of MAPKs pathway in cancer cells

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Huajun Zhao ◽  
Lili Xu ◽  
Zhihui Zhu ◽  
Shasha Tian ◽  
Yingying Wei ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cycle Arrest

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.

Natural compound catechol induces DNA damage, apoptosis, and G1 cell cycle arrest in breast cancer cells

2020 ◽  
Author(s):  
Cijo George Vazhappilly ◽  
Rawad Hodeify ◽  
Shoib Sarwar Siddiqui ◽  
Amina Jamal Laham ◽  
Varsha Menon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Natural Compound ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest
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