title: Excavatolide B inhibits nonsmall cell lung cancer proliferation by altering peroxisome proliferator activated receptor gamma expression and PTEN/AKT/NF-Kβ expression.
abstract: Marine organisms are proven to be rich source of secondary metabolites that can be used to treat various diseases. Excavatolide B (Exc.B), the most abundant metabolite was found in the marine coral Briareum excavatum exhibits cytotoxic effects against lung cancer cell. Treatment of the A549 cells with Exc.B significantly reduced its cell viability and induced cell cycle arrest at subG1 phase in a dose- and time-dependent manner, respectively. Apoptosis induction by Exc.B was further confirmed by decreased pro-caspase 3 expressions and increased proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) expression. Furthermore, Exc.B increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) and also decreased the antioxidant enzymes such as, Catalase, GPx, SOD, GST, and GSH. The proteomic analysis data revealed that total thirty six proteins were altered by Exc.B. STRING database showed that most of the altered proteins have no interaction between each other. Based on these data, KSR1, RuVBL2, PPAR-γ, and Tenascin X proteins were chosen to validate the 2DE data by Western blotting. Additional experiments demonstrated that Exc.B induced PTEN expression and inhibited pAKT and NF-kB expression. These results provide a novel insight into mechanisms underlying the inhibition of A549 cells growth by excavatolide B. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 290-301, 2017.
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, 974, Taiwan.
authors.forename: Bharath Kumar
authors.initials: BK
authors.lastname: Velmurugan
authors.affiliation: Department of Research, Buddhist Tzu Chi General Hospital, General Education Center, Tzu Chi College of Technology, Hualien, Taiwan.
authors.forename: Hsueh-Hui
authors.initials: HH
authors.lastname: Yang
authors.affiliation: Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung, Taiwan.|National Museum of Marine Biology and Aquarium, Pingtung, 944, Taiwan.
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, 974, Taiwan.|Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung, Taiwan.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng
mesh_terms: D000072283:A549 Cells; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000633:toxicity*; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D000975:Antioxidants; D004224:Diterpenes; D016328:NF-kappa B; D047495:PPAR gamma; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C574336:excavatolide B; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053148:Caspase 3
keywords: KSR1; NSCLC; PPAR-γ; RuVBL2; briareum excavatum; excavatolide B; tenascin X