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http://dx.doi.org/10.5352/JLS.2011.21.10.1494

β-Lapachone-Induced Apoptosis is Associated with Inhibition of Cyclooxygenase-2 Activity in Human Lung Cancer A549 Cells  

Choi, Yung-Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine, Department of Biomaterial Control (BK21 program) and Blue-Bio Industry Regional Innovation Center, Dongeui University)
Publication Information
Journal of Life Science / v.21, no.10, 2011 , pp. 1494-1499 More about this Journal
Abstract
${\beta}$-lapachone, a quinone of lapachol extracted from the bark of the lapacho tree, has been found to induce apoptosis in various human cancer cells. In the present study, we investigated further possible mechanisms by which ${\beta}$-lapachone exerts its pro-apoptotic action in cultured human lung cancer A549 cells. ${\beta}$-lapachone treatment resulted in inhibition of growth and induction of apoptosis in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of apoptosis by ${\beta}$-lapachone was associated with up-regulation of the expression of p53 and p21 in both transcriptional and translational levels, and the phosphorylation of p53. In addition, ${\beta}$-lapachone activated caspase-3 and -9, and induced degradation of caspase-3 target proteins such as poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin. Furthermore, ${\beta}$-lapachone treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 synthesis. Taken together, these results indicated that ${\beta}$-lapachone may have therapeutic potential in human lung cancer treatment.
Keywords
${\beta}$-lapachone; apoptosis; p53; p21; COX-2;
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