Betulinic acid, a natural cytotoxic agent, fails to trigger apoptosis in human Burkitt's lymphoma-derived B-cell lines.
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.
Karpova
Maria B
MB
Childhood Cancer Research Unit, Department of Woman and Child Health, Karolinska University Hospital, Stockholm, Sweden.
Sanmun
Duangmanee
D
Henter
Jan-Inge
JI
Smirnov
Aleksandr F
AF
Fadeel
Bengt
B
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D016158:Genes, p53; D006801:Humans; D019169:Jurkat Cells; D016393:Lymphoma, B-Cell / Q000473:pathology*; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000094062:Betulinic Acid
D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D020169:Caspases; D000094062:Betulinic Acid