ArticleCell stress & chaperones2013
Radiosensitization of wildtype p53 cancer cells by the MDM2-inhibitor PXN727 is associated with altered heat shock protein 70 (Hsp70) levels.
Article in Cell stress & chaperones, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- Analysis of p53-Independent Functions of the Mdm2-MdmX Complex Using Data-Independent Acquisition-Based Profiling.Proteomes · 2025Article
- Hypoxia-Induced Cancer Cell Responses Driving Radioresistance of Hypoxic Tumors: Approaches to Targeting and Radiosensitizing.Cancers · 2021Review
- Cellular Mechanism of Gene Mutations and Potential Therapeutic Targets in Ovarian Cancer.Cancer management and research · 2021Review
- Cellular Pathways in Response to Ionizing Radiation and Their Targetability for Tumor Radiosensitization.International journal of molecular sciences · 2016Review
- Inhibition of MDM2 by RG7388 confers hypersensitivity to X-radiation in xenograft models of childhood sarcoma.Pediatric blood & cancer · 2015Article
- Molecular mechanisms of nutlin-3 involve acetylation of p53, histones and heat shock proteins in acute myeloid leukemia.Molecular cancer · 2014Article
- Critical role of aberrant angiogenesis in the development of tumor hypoxia and associated radioresistance.Cancers · 2014Article
- Targeting p53-MDM2-MDMX loop for cancer therapy.Sub-cellular biochemistry · 2014Review
- The MDM2-p53 pathway revisited.Journal of biomedical research · 2013Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The oncoprotein MDM2 (murine double minute 2) is often overexpressed in human tumors and thereby attenuates the function of the tumor suppressor p53. In this study, we investigated the effects of the novel MDM2-inhibitor PXN727 on p53 activation, cell proliferation, cell cycle distribution and radiosensitivity. Since the localization of heat shock protein 70 (Hsp70) exerts different effects on radioresistance of tumor cells, we investigated the impact of PXN727 on intracellular, membrane, and secreted Hsp70 levels. We could show that PXN727 exerts its effects on wildtype p53 (HCT116 p53⁺/⁺, A549) but not p53 depleted (HCT116 p53⁻/⁻) or mutated (FaDu) tumor cells. PXN727 activates p53, induces the expression of p21, reduces the proportion of cells in the radioresistant S-phase and induces senescence. Radiosensitivity was significantly increased by PXN727 in HCT116 p53⁺/⁺ tumor cells. Furthermore, PXN727 causes a downregulation of Hsp70 membrane expression and an upregulated secretion of Hsp70 in wildtype p53 tumor cells. Our data suggest that re-activation of p53 by MDM2-inhibition modulates Hsp70 membrane expression and secretion which might contribute to the radiosensitizing effect of the MDM2-inhibitor PXN727.
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