PMID: 17169485 [PubMed - as supplied by
publisher]
Betulinic acid, a natural
cytotoxic agent, fails to trigger apoptosis in human Burkitt's lymphoma-derived
B-cell lines.
Childhood
Cancer Research Unit, Department of Woman and Child Health, Karolinska
University Hospital , Stockholm , Sweden .
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. Copyright 2005 Wiley-Liss, Inc.
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