FEBS Letters · 2007 · 82 citations · 25 references
Life SciencesCell BiologyPharmacologyApoptosisCancer PharmacologyMitochondrial BiologyApoptosis In CancerApoptosis RegulationApoptotic SignalingBcl-2 Family ProteinsMitochondrial SignalingReactive Oxygen SpeciesBcl-xl FunctionLung AdenocarcinomaMitochondrial Apoptosis PathwaysMitochondrial Cell Death PathwaysMitochondrial Pathway Of ApoptosisOxidative Stress In CancerReactive Oxygen Species GenerationReactive Oxygen Species-induced Apoptosis
Coumarins have attracted intense interest in recent years because they have been identified from natural sources, especially green plants and have diverse pharmacological properties. In this study, we investigated whether 7,8-dihydroxy-4-methylcoumarin (DHMC) caused apoptosis in A549 human non-small cell lung carcinoma cells (NSCLC) and, if so, by what mechanisms. Here, we show that, in A549 human NSCLC cells, DHMC induces apoptosis through mitochondria-mediated caspase-dependent pathway. Although an increase in the levels of reactive oxygen species (ROS) was observed, pre-treatment with antioxidant showed no protective effect against DHMC-induced apoptosis. In addition, our immunoblot data revealed that DHMC treatment led to down-regulation of Bcl-xl, Bax, p21, Cox-2, p53 and upregulation of c-Myc. Results in the present study for the first time suggest that DHMC induces apoptosis in human lung A549 cells through partial inhibition of ERK/MAPK signaling.
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c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release
Philippe Juin, Anne‐Odile Hueber, Trevor D. Littlewood et al. · Genes & Development · 1999 · 334 citations · Full text