Hexamethylene bisacetamide induces programmed cell death (apoptosis) and down-regulates BCL-2 expression in human myeloma cells Journal Article

   


Authors: Siegel, D. S.; Zhang, X.; Feinman, R.; Teitz, T.; Zelenetz, A.; Richon, V. M.; Rifkind, R. A.; Marks, P. A.; Michaeli, J.
Article Title: Hexamethylene bisacetamide induces programmed cell death (apoptosis) and down-regulates BCL-2 expression in human myeloma cells
Abstract: 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.
Keywords: controlled study; protein expression; human cell; doxorubicin; antineoplastic agents; conference paper; cell cycle; protein bcl 2; apoptosis; multiple myeloma; down-regulation; tumor cells, cultured; transfection; immunoenzyme techniques; proto-oncogene proteins c-bcl-2; multidrug resistance; clonogenesis; growth inhibition; dna fragment; nucleosome; glycoprotein p; myeloma cell; hexamethylenebisacetamide; multidrug resistance protein; acetamides; humans; human; priority journal
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 95
Issue: 1
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 1998-01-06
Start Page: 162
End Page: 166
Language: English
DOI: 10.1073/pnas.95.1.162
PUBMED: 9419346
PROVIDER: scopus
PMCID: PMC18160
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0031892734&doi=10.1073%2fpnas.95.1.162&partnerID=40&md5=a55b015ba6b5cf1bc38944acbe4f46e6
Notes: Conference Paper -- Export Date: 12 December 2016 -- Source: Scopus
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MSK Authors
  1. Victoria M Richon
    91 Richon
  2. Joseph Michaeli
    62 Michaeli
  3. Andrew D Zelenetz
    768 Zelenetz
  4. Paul Marks
    186 Marks
  5. Richard Rifkind
    118 Rifkind
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