title: Effects of oxypeucedanin on global gene expression and MAPK signaling pathway in mouse neuroblastoma Neuro-2A cells.
abstract: Oxypeucedanin is a major coumarin aglycone that can be extracted from Ostericum koreanum. Coumarin aglycones have demonstrated various pharmacological effects, including anti-proliferation, anti-inflammation, and anti-pain. In this study, in order to understand the pharmacological properties of oxypeucedanin, we investigated global gene expression alteration in mouse neuroblastoma Neuro-2A cells. Results from the MTT assay indicated no decrease of cell viability up to 100 µM for 24 h. We measured gene expression profiles in Neuro-2A cells treated with either 10 µM or no oxypeucedanin for 24 h. We selected 128 differentially expressed genes (DEGs) for comparison of gene expression profiles by Bonferroni-adjusted p values (p < 0.1). Analysis of Gene Ontology (GO) biological process terms using the DEGs demonstrated the importance of protein metabolism, particularly ribosomal protein synthesis and protein degradation, intramembrane protein trafficking, and electron transport. Treatment with oxypeucedanin resulted in the downregulation of most DEGs for ribosomal protein synthesis and the electron transport chain (ETC). In contrast, most DEGs for protein degradation and cellular trafficking systems were upregulated. In addition, we found five upregulated DEGs for core and regulatory proteins involved in the mitogen-activated protein kinase (MAPK) signaling pathway. Independent translational validation of DEGs for MAPK signaling by immunoblot analysis showed consistent agreement with microarray data. Overall protein levels of Erk2 and p38MAPK were elevated, and their phosphorylated forms were also increased. These functional categories, based on transcriptional alteration and complicated modulation of MAPK signaling, might be underlying mechanisms responsible for the various pharmacological effects of oxypeucedanin.
authors.affiliation: College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
authors.forename: Joon-Seok
authors.initials: JS
authors.lastname: Choi
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Shin
authors.forename: Ki-Sub
authors.initials: KS
authors.lastname: Kwon
authors.forename: Seungwon
authors.initials: S
authors.lastname: Shin
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Choung
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kwon
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Bong-Hwan
authors.initials: BH
authors.lastname: Choi
authors.forename: Cheol-Koo
authors.initials: CK
authors.lastname: Lee
mesh_terms: D000818:Animals; D019661:Apiaceae / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000235:genetics; D011564:Furocoumarins / Q000302:isolation & purification / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D018517:Plant Roots / Q000737:chemistry; D025941:Protein Interaction Mapping; D015854:Up-Regulation / Q000235:genetics
chemical_list: D011564:Furocoumarins; C031535:oxypeucadanin