Document Detail

Bryostatin analogue-induced apoptosis in mantle cell lymphoma cell lines.
MedLine Citation:
PMID:  22465296     Owner:  NLM     Status:  MEDLINE    
The anti-cancer effects of bryostatin-1, a potent diacylglycerol analogue, have traditionally been attributed to its action on protein kinase C. However, we previously documented apoptosis in a B non-Hodgkin lymphoma cell line involving diacylglycerol analogue stimulation of Ras guanyl-releasing protein, a Ras activator, and Bim, a proapoptotic Bcl-2 family protein. To further explore the role of Bim, we examined several Bim-deficient B non-Hodgkin lymphoma cells for their responses to pico, a synthetic bryostatin-1-like compound. The Bim(-) mantle cell lymphoma cell lines Jeko-1, Mino, Sp53, UPN1, and Z138 and the Bim(+) cell line Rec-1, as well as the Burkitt lymphoma cells lines BL2 (Bim(-)) and Daudi (Bim(+)), were examined for their response to pico using assays for proliferation and apoptosis as well as biochemical methods for Ras guanyl-releasing proteins and Bcl-2 family members. With the exception of UPN1, mantle cell lymphoma cell lines underwent pico-induced apoptosis, as did BL2. In some cases, hallmarks of apoptosis were substantially diminished in the presence of mitogen-activated protein kinase kinase inhibitors. Pico treatment generally led to increased expression of proapoptotic Bik, although the absolute levels of Bik varied considerably between cell lines. A pico-resistant variant of Z138 exhibited decreased Bik induction compared to parental Z138 cells. Pico also generally decreased expression of anti-apoptotic Bcl-XL and Mcl1. Although, these changes in Bcl-2 family members seem unlikely to fully account for the differential behavior of the cell lines, our demonstration of a potent apoptotic process in most cell lines derived from mantle cell lymphoma encourages a re-examination of diacylglycerol analogues in the treatment of this subset of B non-Hodgkin lymphoma cases.
Ana Lopez-Campistrous; Xiaohua Song; Adam J Schrier; Paul A Wender; Nancy A Dower; James C Stone
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-28
Journal Detail:
Title:  Experimental hematology     Volume:  40     ISSN:  1873-2399     ISO Abbreviation:  Exp. Hematol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-23     Completed Date:  2012-10-01     Revised Date:  2014-06-17    
Medline Journal Info:
Nlm Unique ID:  0402313     Medline TA:  Exp Hematol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  646-56.e2     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Apoptosis Regulatory Proteins / physiology*
Bryostatins / pharmacology*
Cell Line, Tumor
DNA-Binding Proteins / analysis,  physiology
Extracellular Signal-Regulated MAP Kinases / metabolism
Guanine Nucleotide Exchange Factors / analysis,  physiology
Lymphoma, Mantle-Cell / drug therapy*,  pathology
Membrane Proteins / physiology*
Proto-Oncogene Proteins / physiology*
Proto-Oncogene Proteins c-bcl-2 / analysis
bcl-X Protein / analysis
Grant Support
CA31845/CA/NCI NIH HHS; R01 CA031845/CA/NCI NIH HHS; R37 CA031845/CA/NCI NIH HHS; //Canadian Institutes of Health Research
Reg. No./Substance:
0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/BCL2L1 protein, human; 0/Bcl-2-like protein 11; 0/Bryostatins; 0/DNA-Binding Proteins; 0/Guanine Nucleotide Exchange Factors; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/RASGRP1 protein, human; 0/bcl-X Protein; 37O2X55Y9E/bryostatin 1; EC Signal-Regulated MAP Kinases

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