Parthenolide induces significant apoptosis and production of reactive oxygen species in high-risk pre-B leukemia cells.
We investigated whether parthenolide, the principal bioactive component of the herb feverfew (Tanacetum parthenium) induced apoptosis in pre-B acute lymphoblastic leukemia (ALL) lines, including cells carrying the t(4;11)(q21;q23) chromosomal translocation. Parthenolide induced rapid apoptotic cell death distinguished by loss of nuclear DNA, externalization of cell membrane phosphatidylserine, and depolarization of mitochondrial membranes at concentrations ranging from 5 to 100 microM. Using reactive oxygen species (ROS)-specific dyes, an increase in nitric oxide and superoxide anion was detected in the cells by 4 h after exposure to parthenolide. Parthenolide-induced elevation of hypochlorite anion was observed only in the two t(4;11) lines. These data suggest parthenolide may have potential as a potent and novel therapeutic agent against pre-B ALLs.
Zunino
Susan J
SJ
United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, University of California, Davis, CA 95616, USA. szunino@whnrc.usda.gov
Ducore
Jonathan M
JM
Storms
David H
DH
D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012307:Risk Factors; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C002669:parthenolide; D009569:Nitric Oxide