| Autophagy inhibition sensitizes multiple myeloma cells to 17-dimethylaminoethylamino-17-demethoxygeldanamycin-induced apoptosis. | |
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MedLine Citation:
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PMID: 20667592 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The Hsp90 inhibitor 17DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) is currently undergoing clinical trials as an antitumor drug. We show here that treatment of human multiple myeloma (MM) cells with 17DMAG induces mTOR inhibition and microtubule-associated protein light chain 3 (LC3) conversion (LC3-I to LC3-II), an indicator of autophagy. Interestingly, 17DMAG synergistically induces apoptosis through a mitochondria-operated pathway in the presence of the autophagy inhibitor 3-methyladenine (3-MA). Inhibition of autophagy by 3-MA facilitated caspase activation, cytochrome c release from mitochondria and poly (ADP-ribose) polymerase (PARP) cleavage in myeloma cells treated with 17DMAG. The potential use of Hsp90 and autophagy inhibitors combinations as a therapeutic tool in MM is further discussed in our work. |
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Authors:
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Carmen Palacios; Rosa Martín-Pérez; Ana Isabel López-Pérez; Atanasio Pandiella; Abelardo López-Rivas |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-27 |
Journal Detail:
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Title: Leukemia research Volume: 34 ISSN: 1873-5835 ISO Abbreviation: Leuk. Res. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-09-27 Completed Date: 2010-11-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7706787 Medline TA: Leuk Res Country: England |
Other Details:
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Languages: eng Pagination: 1533-8 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Centro Andaluz de Biología Molecular y Medicina Regenerativa, Consejo Superior de Investigaciones Científicas, Sevilla, Spain. carmen.palacios@cabimer.es |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenine
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analogs & derivatives,
pharmacology Antineoplastic Agents / pharmacology Apoptosis / drug effects* Autophagy / drug effects* Benzoquinones / pharmacology*, therapeutic use HSP90 Heat-Shock Proteins / antagonists & inhibitors Humans Lactams, Macrocyclic / pharmacology*, therapeutic use Mitochondria / metabolism Multiple Myeloma / drug therapy*, pathology |
| Chemical | |
Reg. No./Substance:
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0/17-(dimethylaminoethylamino)-17-demethoxygeldanamycin; 0/Antineoplastic Agents; 0/Benzoquinones; 0/HSP90 Heat-Shock Proteins; 0/Lactams, Macrocyclic; 5142-23-4/3-methyladenine; 73-24-5/Adenine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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