Cr(VI) Induces DNA Damage, Cell Cycle Arrest and Polyploidization: A Flow Cytometric and Comet Assay Study inPisum sativum

2011 ◽  
Vol 24 (7) ◽  
pp. 1040-1047 ◽  
Author(s):  
Eleazar Rodriguez ◽  
Raquel Azevedo ◽  
Pedro Fernandes ◽  
Conceic¸ão Santos
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Comet Assay ◽  
Cell Cycle Arrest ◽  
Damage Cell ◽  
Cycle Arrest ◽  
Flow Cytometric

scholarly journals Tris (1,3-dichloro-2-propyl) phosphate treatment induces DNA damage, cell cycle arrest and apoptosis in murine RAW264.7 macrophages

2019 ◽  
Vol 44 (3) ◽  
pp. 133-144 ◽  
Author(s):  
Wei Zhang ◽  
Ruiguo Wang ◽  
John P. Giesy ◽  
Yang Li ◽  
Peilong Wang
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Damage Cell ◽  
Cycle Arrest ◽  
Raw264.7 Macrophages ◽  
Phosphate Treatment

Celastrol Induced DNA Damage, Cell Cycle Arrest, and Apoptosis in Human Rheumatoid Fibroblast-Like Synovial Cells

2013 ◽  
Vol 41 (03) ◽  
pp. 615-628 ◽  
Author(s):  
Zengtao Xu ◽  
Guosheng Wu ◽  
Xu Wei ◽  
Xiuping Chen ◽  
Yitao Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Inflammatory Diseases ◽  
Annexin V ◽  
Synovial Fibroblasts ◽  
Damage Cell ◽  
Cycle Arrest ◽  
M Phase

Celastrol is one of the principal active ingredients of Tripterygium wilfordii Hook.f., a toxic Chinese medical herb traditionally prescribed for controlling pain and inhibiting inflammation in various chronic inflammatory diseases, including rheumatoid arthritis (RA). Resistance to apoptosis of fibroblast-like synoviocytes is considered a major characteristic of RA. In this study, we test celastrol's cytotoxic effect and potential mechanisms in human rheumatoid synovial fibroblasts (RA-FLS). In the cytotoxic assay, we found that celastrol dose-dependently decreased RA-FLS viability and increased LDH release. The apoptotic nuclear morphology was observed after celastrol treatment as determined by DAPI fluorescence staining. Flow cytometry analysis with PI and Annexin V revealed that celastrol induced RA-FLS cell cycle arrest in the G2/M phase and apoptosis. Furthermore, celastrol dramatically increased expression of Bax/Bcl-2, proteolytic cleavage of Caspase-3, -9, PARP, and decreased expression of FasR. In addition, celastrol treatment resulted in DNA damage. Collectively, we concluded that celastrol inhibits RA-FLS proliferation by inducing DNA damage, cell cycle arrest, and apoptosis in vitro, which might provide data for its application in RA treatment.

scholarly journals MMSET/WHSC1 Enhances DNA Damage Repair Leading To An Increase In Resistance To Chemotherapeutic Agents

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 808-808
Author(s):  
Mrinal Y. Shah ◽  
Eva Martinez ◽  
Relja Popovic ◽  
Teresa Ezponda ◽  
Eliza C. Small ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Repair ◽  
Comet Assay ◽  
Cell Cycle Arrest ◽  
Dna Damage Repair ◽  
Wild Type ◽  
Cycle Arrest ◽  
Histone 3 ◽  
Damage Repair

Abstract MMSET/WHSC1 is a histone methyltransferase (HMT) overexpressed in t(4;14)+ multiple myeloma (MM) patients, and is believed to be the driving factor in the pathogenesis of this subtype of MM. Overexpression of MMSET also occurs in solid cancers, including neuroblastoma, colon and prostate. MMSET overexpression in MM and prostate cells leads to an increase in histone 3 lysine 36 dimethylation (H3K36me2), and a decrease in histone 3 lysine 27 trimethylation (H3K27me3). This altered epigenetic landscape is accompanied by changes in proliferation, gene expression, and chromatin accessibility. Prior work linked methylation of histones, including H3K36, to the ability of cells to undergo DNA damage repair. In addition, t(4;14)+ patients frequently relapse after regimens that include DNA damage-inducing agents, suggesting that MMSET might play a role in DNA damage repair and response. To investigate the role of MMSET in DNA damage repair, we transfected U2OS cells with a linearized vector expressing a neomycin-resistant gene. In the presence of G418, only cells that are able to integrate this plasmid through non-homologous end joining (NHEJ) can survive. siRNA knockdown of MMSET led to a decrease in cell survival, suggesting that MMSET is necessary for efficient DNA repair. We also used U2OS cells engineered to express the AsiSI enzyme fused to an estrogen receptor hormone-binding domain. Upon tamoxifen treatment, double strand breaks (DSBs) are induced at multiple AsiSI recognition sites, accompanied by an increase in γH2AX foci. The extent of repair after AsiSI-induced damage was ascertained by the ability of a DNA fragment that spans a specific cut site to be PCR amplified. With MMSET knockdown, there was a >10 fold increase in unrepaired DNA. ChIP analysis showed that with the depletion of MMSET, γH2AX persisted at the cut site. ChIP for specific effectors of DNA damage showed a marked decrease of recruitment of CtIP and RAD51 to the DSB. However, immunoblot analysis showed that CtIP and RAD51 levels were drastically decreased with MMSET depletion, thus explaining the loss of their recruitment to DSBs. In contrast, XRCC4 levels were maintained with MMSET siRNA, but its recruitment to the DSB decreased. CtIP is important for both NHEJ and homologous recombination (HR), RAD51 is critical for HR, and XRCC4 is necessary for NHEJ, suggesting that MMSET is important in multiple pathways of DNA repair. To study the effect of MMSET in MM, we used the t(4;14)+ KMS11 cell line, NTKO, and genetically matched TKO cells in which the overexpressed MMSET allele was knocked out. NTKO cells have elevated levels of DNA damage at baseline, as measured by a comet assay and by the presence of elevated numbers of 53BP1-positive foci. Upon addition of the DNA damaging agent melphalan, NTKO cells showed increased damage as measured by an increase in the tail moment by the comet assay. Paradoxically, upon treatment of these cells with the DNA damaging agents, NTKO cells survived better than TKO cells. NTKO repaired DNA damage at an enhanced rate and continued to proliferate after a significant DNA damage insult, whereas TKO cells accumulated DNA damage and entered cell cycle arrest. We repleted TKO cells with constructs expressing either wild-type MMSET or an HMT-dead (Y1118A) isoform. Upon treatment, cells expressing the wild-type MMSET have showed enhanced DNA repair and continued proliferation after DNA damage, whereas cells expressing the HMT-dead protein repaired DNA damage more slowly and entered cell cycle arrest. The HMT activity of MMSET was critical for the induction of expression of genes required for multiple DNA repair pathways including CHEK2, DDB2, DDIT3, RAD51, and MRE11, again suggesting that MMSET modulates DNA repair by affecting expression of critical components of the repair machinery. The clinical relevance of these finds becomes more apparent in vivo. Luciferase-tagged KMS11 cells harboring doxycycline-inducible MMSET shRNA were injected into nude mice. After one week, mice were treated with doxycycline and injected with melphalan or saline. Knockdown of MMSET or melphalan treatment alone decreased tumor growth but eventually all mice had progressive disease. Only when MMSET was knocked down and chemotherapy given were the mice rendered tumor free. These findings indicate a new mechanism for the ability of MMSET to enhance DNA repair and identify the protein as a potential therapeutic target in MM and other cancers. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Antiproliferative activity of goniothalamin enantiomers involves DNA damage, cell cycle arrest and apoptosis induction in MCF-7 and HB4a cells

2015 ◽  
Vol 30 (1) ◽  
pp. 250-263 ◽  
Author(s):  
Simone Cristine Semprebon ◽  
Lilian Areal Marques ◽  
Gláucia Fernanda Rocha D'Epiro ◽  
Elaine Aparecida de Camargo ◽  
Glenda Nicioli da Silva ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Antiproliferative Activity ◽  
Apoptosis Induction ◽  
Damage Cell ◽  
Cycle Arrest ◽  
Mcf 7

scholarly journals DNA-damage, cell-cycle arrest and apoptosis induced in BEAS-2B cells by 2-hydroxyethyl methacrylate (HEMA)

2011 ◽  
Vol 723 (2) ◽  
pp. 158-164 ◽  
Author(s):  
V. Ansteinsson ◽  
A. Solhaug ◽  
J.T. Samuelsen ◽  
J.A. Holme ◽  
J.E. Dahl
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Hydroxyethyl Methacrylate ◽  
Damage Cell ◽  
Cycle Arrest

Differences in the Induction of DNA Damage, Cell Cycle Arrest, and Cell Death by 5-Fluorouracil and Antifolates

2001 ◽  
Vol 12 (5) ◽  
pp. 231-239 ◽  
Author(s):  
H.H.J. Backus ◽  
H.M. Pinedo ◽  
D. Wouters ◽  
C.M. Kuiper ◽  
G. Jansen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Death ◽  
Cell Cycle Arrest ◽  
Damage Cell ◽  
Cycle Arrest
Sign in / Sign up

Export Citation Format

Share Document