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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Alternol inhibits proliferation and induces apoptosis in mouse lymphocyte leukemia (L1210) cells
Zhao-Zhe Liu1, Jin Zhu, Bo Sun
1Department of Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100083, PR China.
Abstract:
Alternol is a novel compound purified from the fermenting products by microorganisms named as Alternaria alternata var. monosporus from the bark of Yew. In this study, we tested its effect on mouse lymphocyte leukemia L1210 cells. Alternol was found to inhibit the proliferation and induce apoptosis in L1210 cells. When the cells were treated with Alternol, chromatin condensation and phosphatidylserine externalization were observed with the down-regulation of the pro-survival gene Bcl-2 and the activation of caspase-3, caspase-9, but not caspase-8. Moreover, exposure of cells to Alternol resulted in a significant increase in reactive oxygen species (ROS) and mitochondrial transmembrane potential (DeltaPsim) depolarization. Taken together, these results demonstrate that Alternol is a potent agent in inducing L1210 cells to apoptosis, which involve caspase activation and ROS generation.