Document Detail

Betulinic acid, a natural cytotoxic agent, fails to trigger apoptosis in human Burkitt's lymphoma-derived B-cell lines.
MedLine Citation:
PMID:  16003746     Owner:  NLM     Status:  MEDLINE    
Betulinic acid (BA), a pentacyclic triterpene of natural origin, effectively induces apoptosis in neuroectodermal tumors and was recently shown to be a potent trigger of cell death in human leukemia-derived cell lines. To explore the potential of BA in the treatment of hematologic malignancies, we tested a panel of 10 Burkitt's lymphoma (BL)-derived B-cell lines for sensitivity to BA. The human Jurkat T leukemia cell line was included as a positive control. Our studies show that BA exerts cytotoxic effects in some of the BL cell lines tested, including DG75, a chemoresistant BL cell line. However, cell death was caspase-independent, as evidenced by a lack of protection by zVAD-fmk, a pancaspase inhibitor, and displayed signs of necrosis. Furthermore, BA-induced caspase activation was seen to a minor extent in only 1 of the 10 BL cell lines tested (Ramos, a p53-deficient cell line), but was readily detected in Jurkat cells. Together, these studies indicate that resistance to BA-induced apoptosis is a common feature of BL-derived cell lines.
Maria B Karpova; Duangmanee Sanmun; Jan-Inge Henter; Aleksandr F Smirnov; Bengt Fadeel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  118     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-11-01     Completed Date:  2005-12-13     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  246-52     Citation Subset:  IM    
Copyright Information:
Copyright 2005 Wiley-Liss, Inc.
Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden.
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MeSH Terms
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Burkitt Lymphoma / pathology*
Caspases / metabolism
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
Genes, p53
Jurkat Cells
Lymphoma, B-Cell / pathology*
Triterpenes / pharmacology*
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Triterpenes; 472-15-1/betulinic acid; EC 3.4.22.-/Caspases

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