Parthenolide treatment activates stress signaling proteins in high-risk acute lymphoblastic leukemia cells with chromosomal translocation t(4;11).
Parthenolide, the principal bio-active component of the herb feverfew (Tanacetum parthenium), has shown anti-leukemic activity. We evaluated the cell cycle status and the phosphorylation/activation of proteins involved in signal transduction in t(4;11) and non-t(4;11) acute lymphoblastic leukemia (ALL) cell lines after treatment with parthenolide. The cells were treated with the vehicle or 10 µM parthenolide for 2, 4, 6 and 8 h. As shown by flow cytometric analysis, parthenolide induced growth arrest at the S to G2/M phase transition. Using multiplex technology and Western blotting, we showed that the treatment with parthenolide within 0 to 10 h induced the phosphorylation of stress signaling proteins, including the p38 mitogen-activated protein kinase, the c-Jun N-terminal kinase, c-Jun, the heat shock protein 27 and protein kinase B. These data show that parthenolide induces a stress response leading to cell death and provide further evidence suggesting that parthenolide could be useful as a novel therapeutic agent against high risk ALL with chromosomal translocation t(4;11).
Zunino
Susan J
SJ
United States Department of Agriculture, Western Human Nutrition Research Center, University of California, Davis, CA 95616, USA. susan.zunino@ars.usda.gov
Storms
David H
DH
Ducore
Jonathan M
JM
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002469:Cell Separation; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005434:Flow Cytometry; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014178:Translocation, Genetic
D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C002669:parthenolide