title: 2-Methoxy-1,4-naphthoquinone (MNQ) induces apoptosis of A549 lung adenocarcinoma cells via oxidation-triggered JNK and p38 MAPK signaling pathways.
abstract: OBJECTIVE
  The compound 2-methoxy-1,4-naphthoquinone (MNQ) was previously shown to be cytotoxic against several cancer cell lines, but its mode of action is poorly understood. In this study, we aimed to explore the molecular mechanism of MNQ-induced cytotoxicity of A549 lung adenocarcinoma cells.
  
  
  METHODS
  The growth inhibition potential of MNQ was analyzed using sulforhodamine B assay, flow cytometry cell cycle analysis and Annexin V apoptosis assay. Oxidative stress was determined using 2',7'-dichlorofluorescein diacetate to measure intracellular reactive oxygen species level and comet assay to measure DNA damage. Western blotting was performed to study the activation of mitogen-activated protein kinase signaling pathways.
  
  
  RESULTS
  MNQ induced apoptosis of A549 cells independent of cell cycle arrest, and is mediated by the JNK and p38 MAPK signaling pathways. Further analysis demonstrated that these signaling pathways were stimulated by oxidative DNA damage caused by increased ROS generation in MNQ-treated A549 cells.
  
  
  CONCLUSIONS
  This study is the first to provide an insight into the molecular mechanism of MNQ-induced cytotoxicity of a lung cancer cell, which demonstrates the potential of MNQ as a potential chemotherapeutic drug for lung cancer treatment.
authors.affiliation: School of Biosciences, Taylor's University, No. 1, Jalan Taylor's, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia.
authors.forename: Jeremy Yee Hoong
authors.initials: JY
authors.lastname: Ong
authors.affiliation: School of Biosciences, Taylor's University, No. 1, Jalan Taylor's, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia.
authors.forename: Phelim Voon Chen
authors.initials: PV
authors.lastname: Yong
authors.affiliation: Department of Pre-Clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Lot PT21144, Jalan Sungai Long, Bandar Sungai Long, 43000 Kajang, Selangor Darul Ehsan, Malaysia.
authors.forename: Yang Mooi
authors.initials: YM
authors.lastname: Lim
authors.affiliation: School of Biosciences, Taylor's University, No. 1, Jalan Taylor's, 47500 Subang Jaya, Selangor Darul Ehsan, Malaysia. Electronic address: anthony.ho@taylors.edu.my.
authors.forename: Anthony Siong Hock
authors.initials: AS
authors.lastname: Ho
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000494:pharmacology*; D004249:DNA Damage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009285:Naphthoquinones / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D003603:Cytotoxins; D009285:Naphthoquinones; D009363:Neoplasm Proteins; C096118:2-methoxy-1,4-naphthoquinone; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: 2-Methoxy-1,4-naphthoquinone (MNQ); Lung adenocarcinoma; Mitogen-activated protein kinase (MAPK); Reactive oxygen species (ROS)