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Journal article
Activation of targeted necrosis by a p53 peptide: a novel death pathway that circumvents apoptotic resistance
The Journal of biological chemistry, v 282(37), pp 26675-26686
14 Sep 2007
PMID: 17636258
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cancer cells escape apoptosis by intrinsic or acquired mechanisms of drug resistance. An alternative strategy to circumvent resistance to apoptosis could be through redirection into other death pathways, such as necrosis. However, necrosis is a nonspecific, nontargeted process resulting in cell lysis and inflammation of both cancer and normal cells and is therefore not a viable alternative. Here, we report that a C-terminal peptide of p53, called p53p-Ant, induced targeted necrosis only in multiple mutant p53 human prostate cancer lines and not normal cells, because the mechanism of cytotoxicity by p53p-Ant is dependent on the presence of high levels of mutant p53. Topotecan- and paclitaxel-resistant prostate cancer lines were as sensitive to p53p-Ant-induced targeted necrosis as parental lines. A massive loss of ATP pools and intracellular generation of reactive oxygen species was involved in the mechanism of targeted necrosis, which was inhibited by O(2)(.) scavengers. We hypothesize that targeted necrosis by p53p-Ant is dependent on mutant p53, is mediated by O(2)(.) loss and ATP, and can circumvent chemotherapy resistance to apoptosis. Targeted necrosis, as an alternative pathway for selective killing of cancer cells, may overcome the problems of nonspecificity in utilizing the necrotic pathway.
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Details
- Title
- Activation of targeted necrosis by a p53 peptide: a novel death pathway that circumvents apoptotic resistance
- Creators
- Richard D Dinnen - Columbia UniversityLisa Drew - Columbia UniversityDaniel P Petrylak - Columbia UniversityYuehua Mao - Columbia UniversityNicholas Cassai - SUNY Downstate Health Sciences UniversityJoseph Szmulewicz - SUNY Downstate Health Sciences UniversityPaul Brandt-Rauf - Columbia UniversityRobert L Fine - Columbia University
- Publication Details
- The Journal of biological chemistry, v 282(37), pp 26675-26686
- Publisher
- ASBMB Publications / Elsevier
- Number of pages
- 12
- Grant note
- R01 85828 / PHS HHS R01 OH 07590 / NIOSH CDC HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000249304900006
- Scopus ID
- 2-s2.0-34848900171
- Other Identifier
- 991019323669404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology