دورية أكاديمية
أعرض في EDS

MDM2 Antagonists Counteract Drug-Induced DNA Damage.

التفاصيل البيبلوغرافية
العنوان: MDM2 Antagonists Counteract Drug-Induced DNA Damage.
المؤلفون: Vilgelm AE; Tennessee Valley Healthcare System, Department of Veterans Affairs, Nashville, TN, United States; Vanderbilt University School of Medicine, Department of Cancer Biology, Nashville, TN, United States. Electronic address: anna.e.vilgelm@vanderbilt.edu., Cobb P; Tennessee Valley Healthcare System, Department of Veterans Affairs, Nashville, TN, United States; Vanderbilt University School of Medicine, Department of Cancer Biology, Nashville, TN, United States., Malikayil K; Meharry Medical College, Nashville, TN, United States., Flaherty D; Vanderbilt University Flow Cytometry Shared Resource, Nashville, TN, United States., Andrew Johnson C; Tennessee Valley Healthcare System, Department of Veterans Affairs, Nashville, TN, United States; Vanderbilt University School of Medicine, Department of Cancer Biology, Nashville, TN, United States., Raman D; University of Toledo, Toledo, OH, United States., Saleh N; Tennessee Valley Healthcare System, Department of Veterans Affairs, Nashville, TN, United States; Vanderbilt University School of Medicine, Department of Cancer Biology, Nashville, TN, United States., Higgins B; Pharma Research and Early Development, Roche Innovation Center, New York, NY, United States., Vara BA; Department of Chemistry, Vanderbilt Institute of Chemical Biology, Nashville, TN, United States., Johnston JN; Department of Chemistry, Vanderbilt Institute of Chemical Biology, Nashville, TN, United States., Johnson DB; Division of Hematology and Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States., Kelley MC; Division of Surgical Oncology, Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, United States., Chen SC; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States., Ayers GD; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States., Richmond A; Tennessee Valley Healthcare System, Department of Veterans Affairs, Nashville, TN, United States; Vanderbilt University School of Medicine, Department of Cancer Biology, Nashville, TN, United States.
المصدر: EBioMedicine [EBioMedicine] 2017 Oct; Vol. 24, pp. 43-55. Date of Electronic Publication: 2017 Sep 19.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101647039 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-3964 (Electronic) Linking ISSN: 23523964 NLM ISO Abbreviation: EBioMedicine Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Amsterdam] : Elsevier B.V., [2014]-
مواضيع طبية MeSH: Azepines/*administration & dosage , DNA Damage/*drug effects , Imidazoles/*administration & dosage , Melanoma/*drug therapy , Piperazines/*administration & dosage , Proto-Oncogene Proteins c-mdm2/*antagonists & inhibitors , Pyrimidines/*administration & dosage , Pyrrolidines/*administration & dosage , para-Aminobenzoates/*administration & dosage, Animals ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Azepines/pharmacology ; Cell Line, Tumor ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Replication/drug effects ; HCT116 Cells ; Humans ; Imidazoles/pharmacology ; Melanoma/genetics ; Mice ; Piperazines/pharmacology ; Protein Binding/drug effects ; Proto-Oncogene Proteins c-mdm2/metabolism ; Pyrimidines/pharmacology ; Pyrrolidines/pharmacology ; Tumor Suppressor Protein p53/metabolism ; Xenograft Model Antitumor Assays ; para-Aminobenzoates/pharmacology
مستخلص: Antagonists of MDM2-p53 interaction are emerging anti-cancer drugs utilized in clinical trials for malignancies that rarely mutate p53, including melanoma. We discovered that MDM2-p53 antagonists protect DNA from drug-induced damage in melanoma cells and patient-derived xenografts. Among the tested DNA damaging drugs were various inhibitors of Aurora and Polo-like mitotic kinases, as well as traditional chemotherapy. Mitotic kinase inhibition causes mitotic slippage, DNA re-replication, and polyploidy. Here we show that re-replication of the polyploid genome generates replicative stress which leads to DNA damage. MDM2-p53 antagonists relieve replicative stress via the p53-dependent activation of p21 which inhibits DNA replication. Loss of p21 promoted drug-induced DNA damage in melanoma cells and enhanced anti-tumor activity of therapy combining MDM2 antagonist with mitotic kinase inhibitor in mice. In summary, MDM2 antagonists may reduce DNA damaging effects of anti-cancer drugs if they are administered together, while targeting p21 can improve the efficacy of such combinations.
(Copyright © 2017. Published by Elsevier B.V.)
References: Front Oncol. 2014 May 26;4:123. (PMID: 24904834)
Drug Resist Updat. 2008 Aug-Oct;11(4-5):152-63. (PMID: 18801697)
Cell. 2013 Nov 21;155(5):1088-103. (PMID: 24267891)
Curr Drug Deliv. 2017;14 (5):588-596. (PMID: 28240175)
EMBO Mol Med. 2013 Jan;5(1):149-66. (PMID: 23180582)
Blood. 2008 Oct 1;112(7):2886-95. (PMID: 18633130)
Nat Cell Biol. 2014 Jan;16(1):2-9. (PMID: 24366029)
Nat Rev Drug Discov. 2015 Jun;14(6):405-23. (PMID: 25953507)
Pharmacol Ther. 2017 May;173:67-82. (PMID: 28174095)
Cell Cycle. 2007 Jan 1;6(1):70-4. (PMID: 17245109)
J Leukoc Biol. 2016 Aug;100(2):275-90. (PMID: 27256570)
Cancer Treat Rev. 2016 Nov;50:35-47. (PMID: 27612280)
Nat Commun. 2016 Oct 11;7:13087. (PMID: 27725641)
J Natl Cancer Inst. 2008 Jun 4;100(11):784-95. (PMID: 18505964)
Cell. 2011 Apr 29;145(3):435-46. (PMID: 21529715)
Clin Cancer Res. 2012 Apr 15;18(8):2184-98. (PMID: 22351689)
JAMA Oncol. 2015 Jun;1(3):380-6. (PMID: 26181188)
Cell. 2011 Mar 4;144(5):646-74. (PMID: 21376230)
Cancer Biol Ther. 2013 Mar;14(3):278-85. (PMID: 23298903)
Open Biol. 2015 Mar;5(3):140156. (PMID: 25761368)
Oncoimmunology. 2015 Mar 19;4(8):e1009299. (PMID: 26405565)
Cancer Res. 2014 Sep 15;74(18):5165-72. (PMID: 25070753)
Genes Dev. 1999 Jun 15;13(12):1501-12. (PMID: 10385618)
Cell. 2012 Jul 20;150(2):251-63. (PMID: 22817889)
Sci Signal. 2013 Apr 02;6(269):pl1. (PMID: 23550210)
Cell Death Differ. 2010 Sep;17 (9):1486-500. (PMID: 20203688)
Oncogene. 2013 Aug 8;32(32):3744-53. (PMID: 22945645)
EXCLI J. 2015 Jan 19;14:95-108. (PMID: 26600742)
Cancer Res. 2015 Jan 1;75(1):181-93. (PMID: 25398437)
J Med Genet. 2007 Feb;44(2):99-106. (PMID: 16905682)
Mutagenesis. 1998 Mar;13(2):193-8. (PMID: 9568594)
PLoS One. 2014 Nov 03;9(11):e111060. (PMID: 25365521)
ACS Med Chem Lett. 2013 Apr 02;4(5):466-9. (PMID: 24900694)
J Org Chem. 2013 Nov 1;78(21):10605-16. (PMID: 24127627)
Pharmacol Res. 2016 May;107:111-116. (PMID: 26987942)
Nat Rev Mol Cell Biol. 2004 Jan;5(1):45-54. (PMID: 14708009)
Cancer Res. 2001 Aug 15;61(16):6234-8. (PMID: 11507077)
Clin Cancer Res. 2016 Feb 15;22(4):868-76. (PMID: 26459177)
Oncogene. 2001 Jan 25;20(4):420-9. (PMID: 11313973)
Cancer Res. 2005 Mar 1;65(5):1918-24. (PMID: 15753391)
Cancer Biol Ther. 2011 Nov 1;12(9):827-36. (PMID: 21878748)
Cancer Discov. 2012 May;2(5):401-4. (PMID: 22588877)
Mol Biol Cell. 2012 Feb;23 (4):567-76. (PMID: 22171325)
Front Oncol. 2016 Jan 27;6:7. (PMID: 26858935)
Nat Rev Cancer. 2009 Jun;9(6):400-14. (PMID: 19440234)
Nature. 1992 Mar 19;356(6366):215-21. (PMID: 1552940)
Mol Cell Biol. 1998 Oct;18(10 ):5690-8. (PMID: 9742086)
BMC Cancer. 2010 Feb 23;10 :57. (PMID: 20178585)
Chem Sci. 2011 Jan 1;2(6):1076-1079. (PMID: 22708054)
Proc Natl Acad Sci U S A. 2009 Mar 10;106(10 ):3964-9. (PMID: 19225112)
Cell Rep. 2013 Apr 25;3(4):1252-65. (PMID: 23562156)
معلومات مُعتمدة: U54 CA163069 United States CA NCI NIH HHS; I01 BX002301 United States BX BLRD VA; IK6 BX005225 United States BX BLRD VA; K12 CA090625 United States CA NCI NIH HHS; I01 BX000196 United States BX BLRD VA; P30 CA068485 United States CA NCI NIH HHS; K23 CA204726 United States CA NCI NIH HHS; R01 CA116021 United States CA NCI NIH HHS; R01 GM084333 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: DNA damage; MDM2 antagonist; Melanoma; Mitotic inhibitor; Polyploidy; Replication stress; p21; p53
المشرفين على المادة: 0 (Azepines)
0 (CDKN1A protein, human)
0 (Cyclin-Dependent Kinase Inhibitor p21)
0 (Imidazoles)
0 (MLN 8237)
0 (Piperazines)
0 (Pyrimidines)
0 (Pyrrolidines)
0 (RG7388)
0 (TP53 protein, human)
0 (Tumor Suppressor Protein p53)
0 (para-Aminobenzoates)
53IA0V845C (nutlin 3)
EC 2.3.2.27 (MDM2 protein, human)
EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
تواريخ الأحداث: Date Created: 20171015 Date Completed: 20180618 Latest Revision: 20210227
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5652019
DOI: 10.1016/j.ebiom.2017.09.016
PMID: 29030058
قاعدة البيانات: MEDLINE
الوصف
تدمد:2352-3964
DOI:10.1016/j.ebiom.2017.09.016