Abstract
beta-Lapachone is a naturally occurring quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae) with cancer chemopreventive properties. The objective of the present study was to investigate the effect of beta-lapachone on the cell growth and apoptosis in human colon carcinoma tumor cell line HCT-116. Exposure of HCT-116 cells to beta-lapachone resulted in growth inhibition and induction of apoptosis in a dose-dependent manner as measured by hemocytometer counts, fluorescence microscopy and flow cytometric analysis. This increase in apoptosis was associated with a decrease in Bcl-2 protein expression, an increase in caspase-3 activity, a decrease in intact poly(ADP-ribose) polymerase protein levels and degradation of beta-catenin. After beta-lapachone treatment, the nuclear protein levels of NF-kappaB and the activity of NF-kappaB-DNA binding were markedly decreased. beta-Lapachone treatment also resulted in inhibition of the transcriptional activity of NF-kappaB-luciferase reporter plasmid suggesting that beta-lapachone-induced apoptosis may be partly regulated through the inactivation of NF-kappaB.
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