Eupatorin-Induced Cell Death in Human Leukemia Cells Is Dependent on Caspases and Activates the Mitogen-Activated Protein Kinase Pathway |
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Authors: | Sara Estévez María Teresa Marrero José Quintana Francisco Estévez |
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Institution: | Department of Biochemistry and Molecular Biology, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.; Faculty of Medicine & Health Sciences, United Arab Emirates, |
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Abstract: | Eupatorin is a naturally occurring flavone that inhibits cell proliferation in human tumor cells. Here we demonstrate that eupatorin arrests cells at the G2-M phase of the cell cycle and induces apoptotic cell death involving activation of multiple caspases, mitochondrial release of cytochrome c and poly(ADP-ribose) polymerase cleavage in human leukemia cells. This flavonoid induced the phosphorylation of members of the mitogen-activated protein kinases and cell death was attenuated by inhibition of c-jun N-terminal kinases/stress activated protein kinases. Eupatorin-induced cell death is mediated by both the extrinsic and the intrinsic apoptotic pathways and through a mechanism dependent on reactive oxygen species generation. |
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