Document Detail


Hexamethylene bisacetamide induces programmed cell death (apoptosis) and down-regulates BCL-2 expression in human myeloma cells.
MedLine Citation:
PMID:  9419346     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multiple myeloma (MM) is a B cell malignancy characterized by the expansion of monoclonal Ig-secreting plasma cells with low proliferative activity. It is postulated that inhibition of physiologic cell death is an underlying factor in the pathophysiology of MM. The development of chemoresistance is a common feature in patients with MM. In the present studies, hexamethylene bisacetamide (HMBA), a hybrid polar compound that is a potent inducer of terminal differentiation of various transformed cells, is shown to inhibit the growth of several human myeloma cell lines (ARP-1, U266, and RPMI 8226), including doxorubicin-resistant RPMI 8226 variants that overexpress the multidrug-resistance gene, MDR-1, and its product, p-glycoprotein. In addition to growth arrest and suppression of clonogenicity, HMBA induces apoptosis both in freshly isolated human myeloma cells and in cell lines, as determined by morphologic alterations, cell cycle distribution and endonucleosomal DNA fragmentation. Further, HMBA decreases BCL-2 protein expression in myeloma cells within 12-48 hr. Overexpression of BCL-2 protein in ARP-1 cells confers resistance to HMBA-induced apoptosis. Taken together, these data suggest that HMBA is a potent inducer of apoptosis in human myeloma cells, which may act through suppressing the anti-apoptotic function of the bcl-2 gene. HMBA, and related hybrid polar compounds, may prove useful in the management of this presently incurable disease.
Authors:
D S Siegel; X Zhang; R Feinman; T Teitz; A Zelenetz; V M Richon; R A Rifkind; P A Marks; J Michaeli
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  95     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1998 Jan 
Date Detail:
Created Date:  1998-02-18     Completed Date:  1998-02-18     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  162-6     Citation Subset:  IM    
Affiliation:
Program of Cell Biology, The University of Arkansas, Little Rock, AR 72205, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetamides / pharmacology*
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Down-Regulation* / drug effects
Humans
Immunoenzyme Techniques
Multiple Myeloma / metabolism*
Proto-Oncogene Proteins c-bcl-2 / genetics,  metabolism*
Transfection
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Acetamides; 0/Antineoplastic Agents; 0/Proto-Oncogene Proteins c-bcl-2; 3073-59-4/hexamethylene bisacetamide
Comments/Corrections

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