Betulinic acid-induced apoptosis in leukemia cells.
Betulinic acid (BA), a natural component isolated from Birch trees, effectively induces apoptosis in neuroectodermal and epithelial tumor cells and exerts little toxicity in animal trials. Here, we show that BA-induced marked apoptosis in 65% of primary pediatric acute leukemia cells and all leukemia cell lines tested. When compared for in vitro efficiency with conventionally used cytotoxic drugs, BA was more potent than nine out of 10 standard therapeutics and especially efficient in tumor relapse. No crossresistances were found between BA and any cytotoxic drug. Intracellular apoptosis signaling in leukemia tumor cells paralleled the pathway found in neuroectodermal cells involving caspases, but not death receptors. In isolated mitochondria, BA induced release of both cytochrome c and Smac. Taken together, BA potently induces apoptosis in leukemia cells and should be further evaluated as a future drug to treat leukemia.
Ehrhardt
H
H
Department of Oncology/Hematology, Dr von Haunersches Kinderspital, Lindwurmstr 4, München, Germany.
Fulda
S
S
Führer
M
M
Debatin
K M
KM
Jeremias
I
I
D000293:Adolescent; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D045304:Cytochromes c / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D055502:Secondary Prevention; D015398:Signal Transduction; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000094062:Betulinic Acid
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D045304:Cytochromes c; D020169:Caspases; D000094062:Betulinic Acid