title: Taiwanin A targets non-steroidal anti-inflammatory drug-activated gene-1 in human lung carcinoma.
abstract: Taiwanin A (α,β-bis(piperonylidene)-γ-butyrolactone) is extracted from Taiwania cryptomerioides. Taiwanin A is extracted from tree bark and exhibits antitumor activity in breast, liver, and lung cancer cell lines. The objective of this study was to demonstrate the cytotoxicity of Taiwanin A against tumor cells by increasing the expression of non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1). NAG-1 has been reported to exhibit antitumor and proapoptotic activities, suggesting potential use in cancer therapy. Inhibiting NAG-1 mRNA expression in A549 reduced the cytotoxicity caused by Taiwanin A. Furthermore, the c-Jun-N-terminal kinase/Ste20-related protein proline/alanine-rich kinase (JNK/SPAK) pathway played a key role in the influence of NAG-1 on cell viability, whereas the addition of the JNK pathway inhibitor SP600125 resulted in an inhibitory effect on NAG-1 and recovery of Taiwanin-A-treated cells. A xenograft tumor model demonstrated that Taiwanin A dose-dependently significantly decreases tumor-mediated growth in nude mice by increasing the NAG-1 expression accompanying tumor apoptosis. These data supported the hypothesis that Taiwanin A inhibits lung carcinoma growth by increasing NAG-1 expression through the JNK pathway both in vivo and in vitro. This result can contribute to a compound design for increasing cytotoxicity activity in the future.
authors.affiliation: Department of Pathology, China Medical University & Hospital, Taichung, Taiwan, ROC; Department of Medicine, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Horng-Jyh
authors.initials: HJ
authors.lastname: Harn
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan, R.O.C.
authors.forename: Hong-Meng
authors.initials: HM
authors.lastname: Chuang
authors.affiliation: Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, R.O.C.
authors.forename: Li-Fu
authors.initials: LF
authors.lastname: Chang
authors.affiliation: Department of Pathology, China Medical University & Hospital, Taichung, Taiwan, ROC; Department of Medicine, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Angela Yu Hsuan
authors.initials: AY
authors.lastname: Huang
authors.affiliation: Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, R.O.C.
authors.forename: Shin-Ta
authors.initials: ST
authors.lastname: Hsieh
authors.affiliation: Center for Neuropsychiatry, China Medical University Hospital, Taichung, Taiwan, R.O.C; Department of Neurosurgery, China Medical University Beigan Hospital, Yunlin, Taiwan, R.O.C; Department of Neurosurgery, China Medical University -An Nan Hospital, Tainan, Taiwan, ROC; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Shinn-Zong
authors.initials: SZ
authors.lastname: Lin
authors.affiliation: Department of Department of Cosmeceutics, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Chou
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Life Science and Graduate Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, R.O.C. Electronic address: twchiou@mail.ndhu.edu.tw.
authors.forename: Tzyy-Wen
authors.initials: TW
authors.lastname: Chiou
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D005663:Furans / Q000494:pharmacology*; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000873:Anthracenes; D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D017705:Lignans; C419332:taiwanin A; C432165:pyrazolanthrone; D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Apoptosis; Lung carcinoma; NAG-1; Taiwanin A; c-Jun N-terminal