ArticleOncogene2000
The cytoprotective aminothiol WR1065 activates p21waf-1 and down regulates cell cycle progression through a p53-dependent pathway.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 69 citations in OpenAlex.
- WR1065 conjugated to thiol-PEG polymers as novel anticancer prodrugs: broad spectrum efficacy, synergism, and drug resistance reversal.Frontiers in oncology · 2023Article
- Transition of amyloid/mutant p53 from tumor suppressor to an oncogene and therapeutic approaches to ameliorate metastasis and cancer stemness.Cancer cell international · 2022Review
- Long non-coding RNA BCAR4 aggravated proliferation and migration in esophageal squamous cell carcinoma by negatively regulating p53/p21 signaling pathway.Bioengineered · 2021Article
- PSMC2 knockdown suppressed tumor progression of skin cutaneous melanoma.Cell death discovery · 2021Article
- Multifaceted p21 in carcinogenesis, stemness of tumor and tumor therapy.World journal of stem cells · 2020Review
- Amifostine does not protect thyroid cancer cells in DNA damagingEndocrine connections · 2017Article
- CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Borane-protected phosphines are redox-active radioprotective agents for endothelial cells.Redox biology · 2015Article
- CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Amifostine alleviates radiation-induced lethal small bowel damage via promotion of 14-3-3σ-mediated nuclear p53 accumulation.Oncotarget · 2014Article
- Radioprotection of hematopoietic progenitors by low dose amifostine prophylaxis.International journal of radiation biology · 2014Article
- Comments on the mechanisms of action of radiation protective agents: basis components and their polyvalence.SpringerPlus · 2014Review
- Link between cancer and Alzheimer disease via oxidative stress induced by nitric oxide-dependent mitochondrial DNA overproliferation and deletion.Oxidative medicine and cellular longevity · 2013Review
- The radioprotective agent WR1065 protects cells from radiation damage by regulating the activity of the Tip60 acetyltransferase.International journal of biochemistry and molecular biology · 2011Article
- The cytoprotective drug amifostine modifies both expression and activity of the pro-angiogenic factor VEGF-A.BMC medicine · 2010Article
- Targeting p53 for Novel Anticancer Therapy.Translational oncology · 2010Article
- WR1065 mitigates AZT-ddI-induced mutagenesis and inhibits viral replication.Environmental and molecular mutagenesis · 2009Article
- Amifostine protection against mitomycin-induced chromosomal breakage in fanconi anaemia lymphocytes.Molecules (Basel, Switzerland) · 2008Article
- Article
- Induction of apoptosis in human lung cancer cells following treatment with amifostine and an adenoviral vector containing wild-type p53.Cancer gene therapy · 2006Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The phosphoaminothiol WR1065, the active metabolite of the pro-drug amifostine (WR2721), protects cultured cells and tissues against cytotoxic exposure to radiation or chemotherapeutic agents. We show here that WR1065 and the pro-drug WR2721 activate the p53 tumor suppressor protein and induce the expression of the cyclin-dependent kinase inhibitor p21waf-1 in the breast cancer cell line MCF-7, and in the mouse fibroblast cell line balb/c 3T3. Using two MCF-7 derived cell lines, MN1 and MDD2, we show that induction of p21waf-1 is detectable in MN1 (expressing a functional p53) but not in MDD2 (p53 disabled). These effects are observed at concentrations of WR1065 (0.5 to 1 mM) identical to those required to protect against cytotoxicity by hydrogen peroxide. Induction of p53 is not prevented by addition of aminoguanidine, an inhibitor of Cu-dependent amine-oxidases which blocks the extra-cellular degradation of WR1065 into toxic metabolites. Moreover, spermidine, a natural polyamine structurally related to amifostine, does not activate p53. Induction of p53 by WR1065 results in a delay in the G1/S transition in MCF-7 and MN-1 cells, but not in the p53 disabled cells MDD2. These data indicate that WR1065, a polyamine analog with thiol anti-oxidant properties, activates a cell cycle check-point involving p53.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.