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β-Lapachone-induced reactive oxygen species (ROS) generation mediates autophagic cell death in glioma U87 MG cells.

Park, EJ; Choi, KS; Kwon, TK
Chemico-biological interactions, 189(1-2):37-44, 2011
Journal Title
Chemico-biological interactions
Autophagy is mainly responsible for the degradation of long-lived proteins and subcellular organelles. Autophagy is responsible for the non-apoptotic cell death, and plays a crucial role in regulating cellular functions. β-Lapachone is a quinone-containing compound originally obtained from the lapacho tree in South America. Here, we show that β-lapachone induces death in U87 MG cells, which is not inhibited by blockers of pan-caspase or necrosis. β-Lapachone-induced cell death gradually increased in a time-dependent manner in U87 MG cells, which were partly prevented by pretreatment of a specific inhibitor of NQO1 (dicoumarol). These results suggested that β-lapachone-induced cell death was mediated by NQO1-independent as well as NQO1-dependent cell death pathways. During progression of β-lapachone-induced cell death, translocation and processing of LC3 as well as an increase in acidic vesicular organelles, as assessed by acridine orange staining, were observed. Furthermore, β-lapachone-induced cell death was inhibited by either a knockdown of beclin-1/Atg-6 or Atg-7 gene expression or by autophagy inhibitors (3-methyl adenine or bafilomycin A1). Reactive oxygen species (ROS) were involved in β-lapachone-induced autophagic cell death of U87 MG glioma cells, because β-lapachone induced ROS production and antioxidant N-acetylcysteine (NAC) decreased autophagic cell death. Our results collectively demonstrate that ROS mediate β-lapachone-induced autophagic cell death in U87 MG glioma cells.
MeSH terms
Adenine/analogs & derivatives/pharmacologyAutophagy/*drug effectsBlotting, WesternCell Line, TumorCell Survival/drug effectsEnzyme Inhibitors/pharmacologyFlow CytometryGlioma/*drug therapy/metabolism/pathologyHumansMacrolides/pharmacologyMicroscopy, FluorescenceNAD(P)H Dehydrogenase (Quinone)/antagonists & inhibitors/metabolismNaphthoquinones/*pharmacologyRNA, Small Interfering/administration & dosage/geneticsReactive Oxygen Species/*metabolism
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Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
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