beta-Lapachone-induced apoptosis is associated with activation of caspase-3 and inactivation of NF-kappaB in human colon cancer HCT-116 cells.
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.
Department of Anatomy, Dong-Eui University College of Oriental Medicine and Research Institute of Oriental Medicine, Busan, Korea. choiyh@dongeui.ac.kr
Byung Tae
BT
Choi
JaeHun
J
Cheong
Yung Hyun
YH
Choi
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation; D045325:HCT116 Cells; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009285:Naphthoquinones / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis
D016588:Anticarcinogenic Agents; D016328:NF-kappa B; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; C014638:beta-lapachone; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases