Mechanism of the inhibition of leukemia cell growth and induction of apoptosis through the activation of ATR and PTEN by the topoisomerase inhibitor 3EZ, 20Ac-ingenol

Highlights • 3EZ, 20Ac-ingenol showed characteristics as a topoisomerase catalytic inhibitor, inducing DNA damage. • The alteration of the chromatin structure by the compound induced ATM/AKT and PTEN pathway. • The stabilized p53 by modulating two signaling pathway induced apoptosis via the activati...

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Veröffentlicht in:	Leukemia research 2015-09, Vol.39 (9), p.927-932
Hauptverfasser:	Miyata, Shohei, Fukuda, Yasuaki, Tojima, Haruka, Matsuzaki, Keiichi, Kitanaka, Susumu, Sawada, Hiroshi
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Ataxia Telangiectasia Mutated Proteins - genetics Ataxia Telangiectasia Mutated Proteins - metabolism ATM/ATR Caspase 3 - genetics Caspase 3 - metabolism Cell Cycle - drug effects Cell Line, Tumor Cell Proliferation - drug effects Cyclin-Dependent Kinase Inhibitor p21 - genetics Cyclin-Dependent Kinase Inhibitor p21 - metabolism Diterpenes - pharmacology Gene Expression Regulation, Leukemic Hematology, Oncology and Palliative Medicine Histones - genetics Histones - metabolism Humans Inhibition of proliferation Leukemia p53 Phosphatidylinositol 3-Kinases - genetics Phosphatidylinositol 3-Kinases - metabolism Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism PTEN Phosphohydrolase - agonists PTEN Phosphohydrolase - genetics PTEN Phosphohydrolase - metabolism PTEN/Akt Signal Transduction Topo catalytic inhibitor Topoisomerase Inhibitors - pharmacology Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism
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Zusammenfassung:	Highlights • 3EZ, 20Ac-ingenol showed characteristics as a topoisomerase catalytic inhibitor, inducing DNA damage. • The alteration of the chromatin structure by the compound induced ATM/AKT and PTEN pathway. • The stabilized p53 by modulating two signaling pathway induced apoptosis via the activation of Bcl-2 family genes.
ISSN:	0145-2126 1873-5835
DOI:	10.1016/j.leukres.2015.06.006