Document Detail


Interleukin-6 sensitizes multiple myeloma cell lines for apoptosis induced by interferon-alpha.
MedLine Citation:
PMID:  10720689     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Interleukin-6 (IL-6) is a multifunctional cytokine affecting growth and survival of normal B cell lineage and multiple myeloma cells. To test the hypothesis that IL-6, as well as other hematopoietic growth factors, may enhance apoptosis of target cells, we investigated the effect of IL-6 on myeloma cells in the presence of IFN-alpha, which is prescribed for patients with multiple myeloma. MATERIALS AND METHODS: Four myeloma cell lines, PCM6, NOP-2, U266, RPMI8226 were tested. We determined the induction of apoptosis by flow cytometry, using an FITC-Annexin V. RESULTS: IFN-alpha induced apoptosis on myeloma cell lines, and this apoptosis was further enhanced in the presence of IL-6, via activation of caspase 3. During induction of this apoptosis, the expression of c-Myc and Fas increased. The addition of IL-6 further increased the expression of Fas, but not that of c-Myc. Bcl-2, Bcl-x, and p53 were not affected by the addition of IL-6 and/or IFN-alpha. Addition of a PI-3-K inhibitor interfered with the enhancing effect of IL-6 on the apoptosis induced by IFN-alpha. CONCLUSION: We propose that IL-6 has the death signal, as well as growth promoting effects, and that PI-3-K may play a key role in the induction of apoptosis by IL-6.
Authors:
R Minami; K Muta; C Ilseung; Y Abe; J Nishimura; H Nawata
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Experimental hematology     Volume:  28     ISSN:  0301-472X     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-24     Completed Date:  2000-04-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  244-55     Citation Subset:  IM    
Affiliation:
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan. rrhh@intmed3.med.kyushu-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*,  therapeutic use
Apoptosis / drug effects*
Caspase 3
Caspases / metabolism
Drug Synergism
Flow Cytometry
Humans
Interferon-alpha / pharmacology*,  therapeutic use
Interleukin-6 / pharmacology*,  therapeutic use
Multiple Myeloma / drug therapy,  metabolism,  pathology*
Signal Transduction / drug effects
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Interferon-alpha; 0/Interleukin-6; 0/Tumor Suppressor Protein p53; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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