| RIP kinase is involved in arsenic-induced apoptosis in multiple myeloma cells. | |
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MedLine Citation:
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PMID: 15314284 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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These studies explore the molecular effect of arsenicals on MM cells. Freshly isolated cells derived from patients with advanced, chemo-refractory myeloma as well as human myeloma cell lines, ARP-1, RPMI-8226 and H929 were exposed to the organic arsenical melarsoprol and to the inorganic compound AT. Both agents potently induced apoptosis in myeloma cells. Exposure to 1-5 microM AT or melarsoprol for 6 hours suppressed NF-kappa B DNA binding and enhanced of c-Jun kinase (JNK) activity. Arsenic also activated caspase-3 resulting in the cleavage of poly (ADP-ribose) polymerase (PARP) and Fas/TNF alpha related receptor interacting protein (RIP). In contrast to reported observations in acute promyelocytic leukemia, myeloma cell apoptosis was not associated with either the downregulation of Bcl-2 protein or with alterations in the expression of other Bcl-2 family members, Bax, Bak, Bag, and Bcl-xl. This study first shows that arsenic induces apoptotic signaling in MM through the cleavage of TNF alpha related receptor interacting protein (RIP). RIP is a key downstream protein in FasL/ TNF alpha /TRAIL induced apoptosis and a major antiapoptotic adaptor of pathways through NF-kappa B and JNK. RIP has not been previously characterized in myeloma. This study supports the hypothesis that arsenicals share common mediators (RIP, NF-kappa B, PARP, caspase-3) with death receptor induced apoptosis. These studies provide an important insight into the molecular mechanism of AT induced apoptosis and can be used in the development of adjuvant therapy for MM, presently an incurable disease. |
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Authors:
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O Bajenova; B Tang; R Pearse; R Feinman; B H Childs; J Michaeli |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Apoptosis : an international journal on programmed cell death Volume: 9 ISSN: 1360-8185 ISO Abbreviation: Apoptosis Publication Date: 2004 Sep |
Date Detail:
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Created Date: 2004-08-17 Completed Date: 2005-04-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9712129 Medline TA: Apoptosis Country: United States |
Other Details:
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Languages: eng Pagination: 561-71 Citation Subset: IM |
Affiliation:
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The Myeloma Service, Division of Hematology-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. baj@bu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects,
physiology* Arsenic / pharmacology* Caspase 3 Caspases / metabolism Cell Division / drug effects Cell Line, Tumor Cell Survival / drug effects Enzyme Activation / drug effects Humans Melarsoprol / pharmacology Multiple Myeloma / pathology* NF-kappa B / metabolism |
| Chemical | |
Reg. No./Substance:
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0/NF-kappa B; 494-79-1/Melarsoprol; 7440-38-2/Arsenic; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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