scholarly journals Benchmark Dose Analysis of DNA Damage Biomarker Responses Provides Compound Potency and Adverse Outcome Pathway Information for the Topoisomerase II Inhibitor Class of Compounds

2020 ◽  
Vol 61 (4) ◽  
pp. 396-407
Author(s):  
Ryan P. Wheeldon ◽  
Derek T. Bernacki ◽  
Stephen D. Dertinger ◽  
Steven M. Bryce ◽  
Jeffrey C. Bemis ◽  
...  
Keyword(s):  
Dna Damage ◽  
Topoisomerase Ii ◽  
Adverse Outcome ◽  
Benchmark Dose ◽  
Adverse Outcome Pathway ◽  
Pathway Information ◽  
Topoisomerase Ii Inhibitor

scholarly journals E2F-1 cooperates with topoisomerase II inhibition and DNA damage to selectively augment p53-independent apoptosis.

1997 ◽  
Vol 17 (3) ◽  
pp. 1049-1056 ◽  
Author(s):  
J Nip ◽  
D K Strom ◽  
B E Fee ◽  
G Zambetti ◽  
J L Cleveland ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Cycle Progression ◽  
Topoisomerase Ii ◽  
Chemotherapeutic Agents ◽  
Cytotoxic Agents ◽  
Phase Cell ◽  
Topoisomerase Ii Inhibitor ◽  
Dna Damaging Agents ◽  
Myeloid Progenitor Cells ◽  
Induced Apoptosis

Mutations in the retinoblastoma (pRb) tumor suppressor pathway including its cyclin-cdk regulatory kinases, or cdk inhibitors, are a hallmark of most cancers and allow unrestrained E2F-1 transcription factor activity, which leads to unregulated G1-to-S-phase cell cycle progression. Moderate levels of E2F-1 overexpression are tolerated in interleukin 3 (IL-3)-dependent 32D.3 myeloid progenitor cells, yet this induces apoptosis when these cells are deprived of IL-3. However, when E2F activity is augmented by coexpression of its heterodimeric partner, DP-1, the effects of survival factors are abrogated. To determine whether enforced E2F-1 expression selectively sensitizes cells to cytotoxic agents, we examined the effects of chemotherapeutic agents and radiation used in cancer therapy. E2F-1 overexpression in the myeloid cells preferentially sensitized cells to apoptosis when they were treated with the topoisomerase II inhibitor etoposide. Although E2F-1 alone induces moderate levels of p53 and treatment with drugs markedly increased p53, the deleterious effects of etoposide in E2F-1-overexpressing cells were independent of p53 accumulation. Coexpression of Bcl-2 and E2F-1 in 32D.3 cells protected them from etoposide-mediated apoptosis. However, Bcl-2 also prevented apoptosis of these cells upon exposure to 5-fluorouracil and doxorubicin, which were also cytotoxic for control cells. Pretreating E2F-1-expressing cells with ICRF-193, a second topoisomerase II inhibitor that does not damage DNA, protected the cells from etoposide-induced apoptosis. However, ICRF-193 cooperated with DNA-damaging agents to induce apoptosis. Therefore, topoisomerase II inhibition and DNA damage can cooperate to selectively induce p53-independent apoptosis in cells that have unregulated E2F-1 activity resulting from mutations in the pRb pathway.

Induction of DNA damage and ATF3 by retigeric acid B, a novel topoisomerase II inhibitor, promotes apoptosis in prostate cancer cells

2013 ◽  
Vol 337 (1) ◽  
pp. 66-76 ◽  
Author(s):  
Yongqing Liu ◽  
Fengbin Gao ◽  
Hanming Jiang ◽  
Leilei Niu ◽  
Yiling Bi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Topoisomerase Ii ◽  
Prostate Cancer Cells ◽  
Topoisomerase Ii Inhibitor

DNA damage, c-myc suppression and apoptosis induced by the novel topoisomerase II inhibitor, salvicine, in human breast cancer MCF-7 cells

2004 ◽  
Vol 55 (3) ◽  
pp. 286-294 ◽  
Author(s):  
Hua-Rui Lu ◽  
Ling-Hua Meng ◽  
Min Huang ◽  
Hong Zhu ◽  
Ze-Hong Miao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Human Breast Cancer ◽  
Topoisomerase Ii ◽  
The Novel ◽  
Human Breast ◽  
Topoisomerase Ii Inhibitor ◽  
Mcf 7

scholarly journals The catalytic topoisomerase II inhibitor dexrazoxane induces DNA breaks, ATF3 and the DNA damage response in cancer cells

2015 ◽  
Vol 172 (9) ◽  
pp. 2246-2257 ◽  
Author(s):  
Shiwei Deng ◽  
Tiandong Yan ◽  
Teodora Nikolova ◽  
Dominik Fuhrmann ◽  
Andrea Nemecek ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Dna Damage Response ◽  
Topoisomerase Ii ◽  
Dna Breaks ◽  
Topoisomerase Ii Inhibitor ◽  
Damage Response

A novel epoxypropoxy flavonoid derivative and topoisomerase II inhibitor, MHY336, induces apoptosis in prostate cancer cells

2011 ◽  
Vol 658 (2-3) ◽  
pp. 98-107 ◽  
Author(s):  
Nabanita Patra ◽  
Umasankar De ◽  
Jin-Ah Kang ◽  
Ji Mim Kim ◽  
Mee Young Ahn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Topoisomerase Ii ◽  
Prostate Cancer Cells ◽  
Topoisomerase Ii Inhibitor

scholarly journals Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 180
Author(s):  
Maud Weiss ◽  
Jiahui Fan ◽  
Mickaël Claudel ◽  
Luc Lebeau ◽  
Françoise Pons ◽  
...  
Keyword(s):  
Carbon Dots ◽  
Lung Inflammation ◽  
Adverse Outcome ◽  
Cellular Responses ◽  
Target Cells ◽  
Inflammasome Activation ◽  
Adverse Outcome Pathway ◽  
Acute Lung Inflammation

With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

The effects of gene × environment interactions on silver nanoparticle toxicity in the respiratory system: An adverse outcome pathway

2021 ◽  
Author(s):  
Tyler P. Nicholas ◽  
William K. Boyes ◽  
David K. Scoville ◽  
Tomomi W. Workman ◽  
Terrance J. Kavanagh ◽  
...  
Keyword(s):  
Respiratory System ◽  
Silver Nanoparticle ◽  
Adverse Outcome ◽  
Adverse Outcome Pathway ◽  
Nanoparticle Toxicity ◽  
Gene Environment

scholarly journals Tobacco mosaic virus delivery of mitoxantrone for cancer therapy

Nanoscale ◽  
2018 ◽  
Vol 10 (34) ◽  
pp. 16307-16313 ◽  
Author(s):  
Richard D. Lin ◽  
Nicole F. Steinmetz
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Mouse Model ◽  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Triple Negative Breast Cancer ◽  
Topoisomerase Ii ◽  
Triple Negative ◽  
Topoisomerase Ii Inhibitor ◽  
Virus Delivery

Tobacco mosaic virus-nanoparticle encapsulation of the topoisomerase II inhibitor mitoxantrone enables therapy in a mouse model of triple negative breast cancer.

Stimulation of Topoisomerase II-Mediated DNA Damage via a Mechanism Involving Protein Thiolation†

Biochemistry ◽  
2001 ◽  
Vol 40 (11) ◽  
pp. 3316-3323 ◽  
Author(s):  
Huimin Wang ◽  
Yong Mao ◽  
Allan Y. Chen ◽  
Nai Zhou ◽  
Edmond J. LaVoie ◽  
...  
Keyword(s):  
Dna Damage ◽  
Topoisomerase Ii ◽  
Stimulation Of
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