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Effects of hippuristanol, an inhibitor of eIF4A, on adult T-cell leukemia.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2011 Mar 15; Vol. 81 (6), pp. 713-22. Date of Electronic Publication: 2011 Jan 08. - Publication Year :
- 2011
-
Abstract
- We evaluated the anti-adult T-cell leukemia (ATL) effects of hippuristanol, an eukaryotic translation initiation inhibitor from the coral Isis hippuris. Hippuristanol inhibited proliferation of HTLV-1-infected T-cell lines and ATL cells, but not normal peripheral blood mononuclear cells. It induced cell cycle arrest during G₁ phase by reducing the expression of cyclin D1, cyclin D2, CDK4 and CDK6, and induced apoptosis by reducing the expression of Bcl-x(L), c-IAP2, XIAP and c-FLIP. The induced apoptosis was associated with activation of caspase-3, -8 and -9. Hippuristanol also suppressed IkappaBalpha phosphorylation and depleted IKKalpha, IKKgamma, JunB and JunD, resulting in inactivation of NF-kappaB and AP-1. It also suppressed carbonic anhydrase type II expression. In addition to its in vitro effects, hippuristanol suppressed tumor growth in mice with severe combined immunodeficiency harboring tumors induced by inoculation of HTLV-1-infected T cells. These preclinical data suggest that hippuristanol could be a potentially useful therapeutic agent for patients with ATL.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Apoptosis drug effects
Apoptosis physiology
Cell Line, Transformed
Cell Line, Tumor
Cells, Cultured
DEAD-box RNA Helicases metabolism
Enzyme Inhibitors therapeutic use
Eukaryotic Initiation Factor-4A
Female
Human T-lymphotropic virus 1 drug effects
Human T-lymphotropic virus 1 physiology
Humans
Leukemia-Lymphoma, Adult T-Cell metabolism
Leukemia-Lymphoma, Adult T-Cell pathology
Mice
Mice, Inbred ICR
Mice, SCID
Sterols therapeutic use
DEAD-box RNA Helicases antagonists & inhibitors
Enzyme Inhibitors pharmacology
Leukemia-Lymphoma, Adult T-Cell drug therapy
Sterols pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2968
- Volume :
- 81
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21219881
- Full Text :
- https://doi.org/10.1016/j.bcp.2010.12.025