Premium
Betulinic acid, a natural cytotoxic agent, fails to trigger apoptosis in human Burkitt's lymphoma‐derived B‐cell lines
Author(s) -
Karpova Maria B.,
Sanmun Duangmanee,
Henter JanInge,
Smirnov Aleksandr F.,
Fadeel Bengt
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21311
Subject(s) - jurkat cells , cell culture , apoptosis , cytotoxic t cell , betulinic acid , programmed cell death , leukemia , biology , lymphoma , cancer research , cytotoxicity , immunology , t cell , biochemistry , in vitro , immune system , genetics
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. © 2005 Wiley‐Liss, Inc.