Planta Med 2011; 77(13): 1512-1518
DOI: 10.1055/s-0030-1270917
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Effects of Oxypeucedanin on Global Gene Expression and MAPK Signaling Pathway in Mouse Neuroblastoma Neuro-2A Cells

Joon-Seok Choi1 , Hyun-Young Shin1 , Ki-Sub Kwon1 , Seungwon Shin2 , Se-Young Choung3 , Yong-Soo Kwon 4 , Jae-Won Lee5 , Bong-Hwan Choi6 , Cheol-Koo Lee1
  • 1College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
  • 2College of Pharmacy, Duksung Women's University, Seoul, Republic of Korea
  • 3College of Pharmacy, KyungHee University, Seoul, Republic of Korea
  • 4College of Pharmacy, Kang Won National University, Chuncheon, Republic of Korea
  • 5Department of Statistics, College of Political Science and Economics, Korea University, Seoul, Republic of Korea
  • 6Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration, Suwon, Republic of Korea
Further Information

Publication History

received Dec. 28, 2010 revised February 13, 2011

accepted February 16, 2011

Publication Date:
21 March 2011 (online)

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.

References

  • 1 Chi H J, Kim H S. Studies on essential oils of plants of Angelica kenus in Korea.  Korean J Pharmacognosy. 1993;  24 111-115
  • 2 Kwon Y S, In K K, Kim C M. Chemical constituents from the roots of Ostericum koreanum.  Korean J Pharmacognosy. 2000;  31 287-294
  • 3 Choi H Y, Guh Y, Ham I. Comparision with essential oils of Angelicae koreanae Radix.  Korean J Herbol. 2004;  19 169-178
  • 4 Kim C M, Heo M Y, Kim H P, Sin K S, Pachaly P. Pharmacological activities of water extracts of Umbelliferae plants.  Arch Pharm Res. 1991;  14 87-92
  • 5 Lee S K, Cho H K, Cho S H, Kim S S, Nahm D H, Park H S. Occupational asthma and rhinitis caused by multiple herbal agents in a pharmacist.  Ann Allergy Asthma Immunol. 2001;  86 469-474
  • 6 Kang T J, Lee S Y, Singh R P, Agarwal R, Yim D S. Anti-tumor activity of oxypeucedanin from Ostericum koreanum against human prostate carcinoma DU145 cells.  Acta Oncol. 2009;  48 895-900
  • 7 Lee Y Y, Lee S, Jin J L, Yun-Choi H S. Platelet anti-aggregatory effects of coumarins from the roots of Angelica genuflexa and A. gigas.  Arch Pharm Res. 2003;  26 723-726
  • 8 Fujioka T, Furumi K, Fujii H, Okabe H, Mihashi K, Nakano Y, Matsunaga H, Katano M, Mori M. Antiproliferative constituents from Umbelliferae plants. V. A new furanocoumarin and falcarindiol furanocoumarin ethers from the root of Angelica japonica.  Chem Pharm Bull (Tokyo). 1999;  47 96-100
  • 9 Kim Y K, Kim Y S, Ryu S Y. Antiproliferative effect of furanocoumarins from the root of Angelica dahurica on cultured human tumor cell lines.  Phytother Res. 2007;  21 288-290
  • 10 Ban H S, Lim S S, Suzuki K, Jung S H, Lee S, Lee Y S, Shin K H, Ohuchi K. Inhibitory effects of furanocoumarins isolated from the roots of Angelica dahurica on prostaglandin E2 production.  Planta Med. 2003;  69 408-412
  • 11 Matsuda H, Morikawa T, Ohgushi T, Ishiwada T, Nishida N, Yoshikawa M. Inhibitors of nitric oxide production from the flowers of Angelica furcijuga: structures of hyuganosides IV and V.  Chem Pharm Bull (Tokyo). 2005;  53 387-392
  • 12 Marston A, Hostettmann K, Msonthi J D. Isolation of antifungal and larvicidal constituents of Diplolophium buchanani by centrifugal partition chromatography.  J Nat Prod. 1995;  58 128-130
  • 13 Widelski J, Popova M, Graikou K, Glowniak K, Chinou I. Coumarins from Angelica lucida L.–antibacterial activities.  Molecules. 2009;  14 2729-2734
  • 14 Kimura Y, Ohminami H, Arichi H, Okuda H, Baba K, Kozawa M, Arichi S. Effects of various coumarins from roots of Angelica dahurica on actions of adrenaline, ACTH and insulin in fat cells.  Planta Med. 1982;  45 183-187
  • 15 Seo E K, Kim K H, Kim M K, Cho M H, Choi E, Kim K, Mar W. Inhibitors of 5alpha-reductase type I in LNCaP cells from the roots of Angelica koreana.  Planta Med. 2002;  68 162-163
  • 16 Kim D K, Lim J P, Yang J H, Eom D O, Eun J S, Leem K H. Acetylcholinesterase inhibitors from the roots of Angelica dahurica.  Arch Pharm Res. 2002;  25 856-859
  • 17 Eun J S, Park J A, Choi B H, Cho S K, Kim D K, Kwak Y G. Effects of oxypeucedanin on hKv1.5 and action potential duration.  Biol Pharm Bull. 2005;  28 657-660
  • 18 Wei Y, Ito Y. Preparative isolation of imperatorin, oxypeucedanin and isoimperatorin from traditional Chinese herb “bai zhi” Angelica dahurica (Fisch. ex Hoffm) Benth. et Hook using multidimensional high-speed counter-current chromatography.  J Chromatogr A. 2006;  1115 112-117
  • 19 Cho R J, Campbell M J. Transcription, genomes, function.  Trends Genet. 2000;  16 409-415
  • 20 Hill K, Model K, Ryan M T, Dietmeier K, Martin F, Wagner R, Pfanner N. Tom40 forms the hydrophilic channel of the mitochondrial import pore for preproteins [see comment].  Nature. 1998;  395 516-521
  • 21 Mokranjac D, Bourenkov G, Hell K, Neupert W, Groll M. Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor.  EMBO J. 2006;  25 4675-4685
  • 22 Lazaris-Karatzas A, Montine K S, Sonenberg N. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5′ cap.  Nature. 1990;  345 544-547
  • 23 Lazaris-Karatzas A, Sonenberg N. The mRNA 5′ cap-binding protein, eIF-4E, cooperates with v-myc or E1A in the transformation of primary rodent fibroblasts.  Mol Cell Biol. 1992;  12 1234-1238
  • 24 Silvera D, Arju R, Darvishian F, Levine P H, Zolfaghari L, Goldberg J, Hochman T, Formenti S C, Schneider R J. Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer.  Nat Cell Biol. 2009;  11 903-908
  • 25 Lee Y S, Wurster R D. Effects of antioxidants on the anti-proliferation induced by protein synthesis inhibitors in human brain tumor cells.  Cancer Lett. 1995;  93 157-163
  • 26 Wimberly B T. The use of ribosomal crystal structures in antibiotic drug design.  Curr Opin Investig Drugs. 2009;  10 750-765
  • 27 Puri M, Kaur I, Kanwar R K, Gupta R C, Chauhan A, Kanwar J R. Ribosome inactivating proteins (RIPs) from Momordica charantia for anti viral therapy.  Curr Mol Med. 2009;  9 1080-1094
  • 28 Dias N, Bailly C. Drugs targeting mitochondrial functions to control tumor cell growth.  Biochem Pharmacol. 2005;  70 1-12
  • 29 Lewis T S, Shapiro P S, Ahn N G. Signal transduction through MAP kinase cascades.  Adv Cancer Res. 1998;  74 49-139
  • 30 Cohen P. The search for physiological substrates of MAP and SAP kinases in mammalian cells.  Trends Cell Biol. 1997;  7 353-361
  • 31 Marshall C J. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase.  Curr Opin Genet Dev. 1994;  4 82-89
  • 32 Im J S, Lee J K. ATR-dependent activation of p 38 MAP kinase is responsible for apoptotic cell death in cells depleted of Cdc7.  J Biol Chem. 2008;  283 25171-25177
  • 33 Tan H, Ling H, He J, Yi L, Zhou J, Lin M, Su Q. Inhibition of ERK and activation of p 38 are involved in diallyl disulfide induced apoptosis of leukemia HL-60 cells.  Arch Pharm Res. 2008;  31 786-793
  • 34 Dean J L, Sully G, Clark A R, Saklatvala J. The involvement of AU-rich element-binding proteins in p 38 mitogen-activated protein kinase pathway-mediated mRNA stabilisation.  Cell Signal. 2004;  16 1113-1121
  • 35 Chambard J C, Lefloch R, Pouyssegur J, Lenormand P. ERK implication in cell cycle regulation.  Biochim Biophys Acta. 2007;  1773 1299-1310

Cheol-Koo Lee

318 West Building, College of Life Sciences and Biotechnology
Korea University

Anam-dong, Seongbuk-gu

Seoul 136-713

Republic of Korea

Phone: +82 2 32 90 30 08

Fax: +82 29 21 17 15

Email: cklee2005@korea.ac.kr

>