Induction of p53 by the concerted actions of aziridine and quinone moieties of diaziquone

Chemical Research in Toxicology
E O NgoP L Gutiérrez

Abstract

The biologic functions attributed to the nucleophosphoprotein p53 have been increasing in recent years. Some studies suggested that wild type p53 is responsible for cell cycle arrest brought about as a response to exposure of mammalian cells to DNA-damaging agents. This cell cycle arrest occurs in order for cells to repair the damaged macromolecules. Extensively damaged cells are also thought to undergo apoptosis via the p53-dependent or -independent signal transduction pathways. In this study, we investigated the ability of diaziridinylbenzoquinones to increase p53 levels in the human breast cancer cell line MCF-7. Diaziquone (AZQ), an anticancer agent, and its derivatives, diaziridinequinone (DZQ) and methyldiaziridinequinone (MeDZQ), induced p53 in a dose- and time-dependent manner as measured by the electrophoretic mobility shift assay. Wild type p53 induction by AZQ was suppressed when DT-diaphorase activity was inhibited by pretreating the cells with dicumarol. Aside from their potent alkylating activity, these agents also undergo redox cycling as evidenced by oxygen consumption and the production of reactive oxygen species (ROS). Inhibition of ROS production by the antioxidant enzyme catalase reduced AZQ- and DZQ-mediate...Continue Reading

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Citations

Jul 13, 2004·Cancer Treatment Reviews·S DansonM Ranson
Dec 3, 2015·Chemical Research in Toxicology·Aurimas StulpinasAudronė Valerija Kalvelytė
Feb 28, 2002·Redox Report : Communications in Free Radical Research·P A AmstadP L Gutierrez
Jun 26, 2013·Acta Crystallographica. Section E, Structure Reports Online·V GaumetV P Zaitsev
Sep 28, 2020·Medicinal Research Reviews·Junmin ZhangJianguo Fang
Sep 15, 2005·The Journal of Biological Chemistry·Dashnamoorthy RaviKumuda C Das

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis