دورية أكاديمية
أعرض في EDS

Additive effects of vorinostat and MLN8237 in pediatric leukemia, medulloblastoma, and neuroblastoma cell lines.

التفاصيل البيبلوغرافية
العنوان: Additive effects of vorinostat and MLN8237 in pediatric leukemia, medulloblastoma, and neuroblastoma cell lines.
المؤلفون: Muscal JA; Texas Children's Cancer Center, Baylor College of Medicine, 1102 Bates Street, Suite 1220, Houston, TX 77030, USA. jamuscal@txch.org, Scorsone KA, Zhang L, Ecsedy JA, Berg SL
المصدر: Investigational new drugs [Invest New Drugs] 2013 Feb; Vol. 31 (1), pp. 39-45. Date of Electronic Publication: 2012 Jun 06.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: United States NLM ID: 8309330 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-0646 (Electronic) Linking ISSN: 01676997 NLM ISO Abbreviation: Invest New Drugs Subsets: MEDLINE
أسماء مطبوعة: Publication: New York : Springer
Original Publication: Boston : M. Nijhoff, 1983-
مواضيع طبية MeSH: Antineoplastic Agents/*administration & dosage , Azepines/*administration & dosage , Histone Deacetylase Inhibitors/*administration & dosage , Hydroxamic Acids/*administration & dosage , Protein Kinase Inhibitors/*administration & dosage , Protein Serine-Threonine Kinases/*antagonists & inhibitors , Pyrimidines/*administration & dosage, Aurora Kinase B ; Aurora Kinases ; Cell Line, Tumor ; Cell Survival/drug effects ; Drug Interactions ; Humans ; Leukemia/drug therapy ; Leukemia/enzymology ; Medulloblastoma/drug therapy ; Medulloblastoma/enzymology ; Neuroblastoma/drug therapy ; Neuroblastoma/enzymology ; Protein Serine-Threonine Kinases/metabolism ; Vorinostat
مستخلص: Purpose: Histone deacetylase (HDAC) inhibitors, such as vorinostat, decrease Aurora kinase activity by a variety of mechanisms. Vorinostat and MLN8237, a selective Aurora A kinase inhibitor, disrupt the spindle assembly and the mitotic checkpoint at different points, suggesting that the combination could have increased antitumor activity. The purpose of this study was to determine the cytotoxicity of vorinostat and MLN8237 in pediatric tumor cell lines.
Methods: Cell survival was measured after 72 h of drug treatment using a modified methyl tetrazolium assay. For drug combination experiments, cells were exposed to medium alone (controls), single drug alone, or to different concentrations of the combination of the two drugs, for a total of 36 concentration pairs per plate. The interaction of the drug combination was analyzed using the universal response surface approach.
Results: The cells express the target of MLN8237, Aurora A. For each cell line, the single agent IC(50) for MLN8237 and for vorinostat was in the clinically relevant range. Both drugs inhibited cell survival in a concentration-dependent fashion. At concentrations of MLN8237 exceeding approximately 1 μM, there was a paradoxical increase in viability signal in all three lines that may be explained by inhibition of Aurora B kinase. The combination of MLN8237 and vorinostat showed additive cytotoxicity in all three cell lines and nearly abrogated the paradoxical increase in survival noted at high single-agent MLN8237 concentrations.
Conclusion: MLN8237 and vorinostat are active in vitro against cancer cell lines. These results provide important preclinical support for the development of future clinical studies of MLN8237and vorinostat.
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معلومات مُعتمدة: K12 CA090433 United States CA NCI NIH HHS; 5K12CA90433-09 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Azepines)
0 (Histone Deacetylase Inhibitors)
0 (Hydroxamic Acids)
0 (MLN 8237)
0 (Protein Kinase Inhibitors)
0 (Pyrimidines)
58IFB293JI (Vorinostat)
EC 2.7.11.1 (AURKB protein, human)
EC 2.7.11.1 (Aurora Kinase B)
EC 2.7.11.1 (Aurora Kinases)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
تواريخ الأحداث: Date Created: 20120607 Date Completed: 20130731 Latest Revision: 20211203
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3655801
DOI: 10.1007/s10637-012-9831-9
PMID: 22669335
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-0646
DOI:10.1007/s10637-012-9831-9