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Connecting the Dots: From DNA Damage and Repair to Aging
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The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival?

Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
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Author to whom correspondence should be addressed.
Academic Editor: Guillermo T. Sáez
Int. J. Mol. Sci. 2016, 17(5), 708; https://doi.org/10.3390/ijms17050708
Received: 28 March 2016 / Revised: 25 April 2016 / Accepted: 3 May 2016 / Published: 11 May 2016
(This article belongs to the Special Issue DNA Damage and Repair in Degenerative Diseases 2016)
It is widely stated that wild-type p53 either mediates the activation of cell cycle checkpoints to facilitate DNA repair and promote cell survival, or orchestrates apoptotic cell death following exposure to cancer therapeutic agents. This reigning paradigm has been challenged by numerous discoveries with different human cell types, including solid tumor-derived cell lines. Thus, activation of the p53 signaling pathway by ionizing radiation and other DNA-damaging agents hinders apoptosis and triggers growth arrest (e.g., through premature senescence) in some genetic backgrounds; such growth arrested cells remain viable, secrete growth-promoting factors, and give rise to progeny with stem cell-like properties. In addition, caspase 3, which is best known for its role in the execution phase of apoptosis, has been recently reported to facilitate (rather than suppress) DNA damage-induced genomic instability and carcinogenesis. This observation is consistent with an earlier report demonstrating that caspase 3 mediates secretion of the pro-survival factor prostaglandin E2, which in turn promotes enrichment of tumor repopulating cells. In this article, we review these and related discoveries and point out novel cancer therapeutic strategies. One of our objectives is to demonstrate the growing complexity of the DNA damage response beyond the conventional “repair and survive, or die” hypothesis. View Full-Text
Keywords: Caspase 3; p21WAF1 (CDKN1A); prostaglandin E2; DNA damage response; ionizing radiation; DNA double-strand breaks; γH2AX foci; apoptosis; premature senescence; multinucleation Caspase 3; p21WAF1 (CDKN1A); prostaglandin E2; DNA damage response; ionizing radiation; DNA double-strand breaks; γH2AX foci; apoptosis; premature senescence; multinucleation
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MDPI and ACS Style

Mirzayans, R.; Andrais, B.; Kumar, P.; Murray, D. The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival? Int. J. Mol. Sci. 2016, 17, 708.

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