Abstract |
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.
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Authors | Maria B Karpova, Duangmanee Sanmun, Jan-Inge Henter, Aleksandr F Smirnov, Bengt Fadeel |
Journal | International journal of cancer
(Int J Cancer)
Vol. 118
Issue 1
Pg. 246-52
(Jan 01 2006)
ISSN: 0020-7136 [Print] United States |
PMID | 16003746
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2005 Wiley-Liss, Inc. |
Chemical References |
- Antineoplastic Agents, Phytogenic
- Pentacyclic Triterpenes
- Triterpenes
- Caspases
- Betulinic Acid
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Topics |
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Burkitt Lymphoma
(pathology)
- Caspases
(metabolism)
- Drug Resistance, Neoplasm
- Drug Screening Assays, Antitumor
- Genes, p53
- Humans
- Jurkat Cells
- Lymphoma, B-Cell
(pathology)
- Pentacyclic Triterpenes
- Triterpenes
(pharmacology)
- Tumor Cells, Cultured
- Betulinic Acid
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