File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: 2-Methoxyestradiol induces endoreduplication through the induction of mitochondrial oxidative stress and the activation of MAPK signaling pathways

Title2-Methoxyestradiol induces endoreduplication through the induction of mitochondrial oxidative stress and the activation of MAPK signaling pathways
Authors
Keywords2-Methoxyestradiol
Endoreduplication
MAPK signaling pathways
Mitochondria
Nasopharyngeal carcinoma
Oxidative stress
Issue Date2010
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharm
Citation
Biochemical Pharmacology, 2010, v. 79 n. 6, p. 825-841 How to Cite?
Abstract2-Methoxyestradiol (2ME2) is a normal physiological metabolite of 17β-estradiol with anti-proliferative and anti-angiogenic activities. The purpose of this study is to elucidate the mechanism whereby 2ME2 induces endoreduplication of the well-differentiated nasopharyngeal carcinoma (NPC) cells. We report here that 2ME2 induces G2/M phase cell cycle arrest followed by endoreduplication of the well-differentiated HK-1 cells. The increase in chromosome number was confirmed by cytogenetic study. Analysis of stress signaling pathways revealed the phosphorylation activation of ERK, JNK and p38 MAPKs at various times after 2ME2 treatment. Pre-treatment of 2ME2-treated HK-1 cells with JNK inhibitor (SP600125), ERK inhibitor (PD98059) and p38 MAPK inhibitor (SB203580) resulted in the reduction of endoreduplicating cells. Furthermore, the increase in the phosphorylation of JNK was accompanied by an increase in the reactive oxygen species. In addition, endoreduplication was observed in cells after treatment with superoxide donor, 2,3-dimethoxy-1,4-naphoquinone (DMNQ). Confocal microscopic analysis also revealed the increase in mitochondrial superoxide anion in 2ME2-treated HK-1 cells. Pre-treatment of HK-1 cells with superoxide dismutase mimetic 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or overexpressing the mitochondrial enzyme MnSOD resulted in the reduction of phosphorylation of JNK and the formation of endoreduplicating cells. Furthermore, the tubulin filaments in cytoplasm remain intact in 2ME2-treated HK-1 cells after pre-treatment of TEMPO. Our results suggest that 2ME2 induces endoreduplication through the induction of oxidative stress and the activation of MAPK signal pathways. The biological significance of drug-induced endoreduplication will also be discussed. © 2009 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/71985
ISSN
2015 Impact Factor: 5.091
2015 SCImago Journal Rankings: 2.263
ISI Accession Number ID
Funding AgencyGrant Number
HKBUFRG2/08-09/076
FSRS/07-08/02
RGCHKBU 1/06C
Funding Information:

This study was partly supported by the following grants: HKBU (FRG2/08-09/076 and FSRS/07-08/02) and RGC (HKBU 1/06C).

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorTing, CMen_HK
dc.contributor.authorLee, YMen_HK
dc.contributor.authorWong, CKCen_HK
dc.contributor.authorWong, ASen_HK
dc.contributor.authorLung, HLen_HK
dc.contributor.authorLung, MLen_HK
dc.contributor.authorLo, KWen_HK
dc.contributor.authorWong, RNSen_HK
dc.contributor.authorMak, NKen_HK
dc.date.accessioned2010-09-06T06:37:11Z-
dc.date.available2010-09-06T06:37:11Z-
dc.date.issued2010en_HK
dc.identifier.citationBiochemical Pharmacology, 2010, v. 79 n. 6, p. 825-841en_HK
dc.identifier.issn0006-2952en_HK
dc.identifier.urihttp://hdl.handle.net/10722/71985-
dc.description.abstract2-Methoxyestradiol (2ME2) is a normal physiological metabolite of 17β-estradiol with anti-proliferative and anti-angiogenic activities. The purpose of this study is to elucidate the mechanism whereby 2ME2 induces endoreduplication of the well-differentiated nasopharyngeal carcinoma (NPC) cells. We report here that 2ME2 induces G2/M phase cell cycle arrest followed by endoreduplication of the well-differentiated HK-1 cells. The increase in chromosome number was confirmed by cytogenetic study. Analysis of stress signaling pathways revealed the phosphorylation activation of ERK, JNK and p38 MAPKs at various times after 2ME2 treatment. Pre-treatment of 2ME2-treated HK-1 cells with JNK inhibitor (SP600125), ERK inhibitor (PD98059) and p38 MAPK inhibitor (SB203580) resulted in the reduction of endoreduplicating cells. Furthermore, the increase in the phosphorylation of JNK was accompanied by an increase in the reactive oxygen species. In addition, endoreduplication was observed in cells after treatment with superoxide donor, 2,3-dimethoxy-1,4-naphoquinone (DMNQ). Confocal microscopic analysis also revealed the increase in mitochondrial superoxide anion in 2ME2-treated HK-1 cells. Pre-treatment of HK-1 cells with superoxide dismutase mimetic 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or overexpressing the mitochondrial enzyme MnSOD resulted in the reduction of phosphorylation of JNK and the formation of endoreduplicating cells. Furthermore, the tubulin filaments in cytoplasm remain intact in 2ME2-treated HK-1 cells after pre-treatment of TEMPO. Our results suggest that 2ME2 induces endoreduplication through the induction of oxidative stress and the activation of MAPK signal pathways. The biological significance of drug-induced endoreduplication will also be discussed. © 2009 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biochempharmen_HK
dc.relation.ispartofBiochemical Pharmacologyen_HK
dc.rightsBiochemical Pharmacology. Copyright © Elsevier Inc.en_HK
dc.subject2-Methoxyestradiol-
dc.subjectEndoreduplication-
dc.subjectMAPK signaling pathways-
dc.subjectMitochondria-
dc.subjectNasopharyngeal carcinoma-
dc.subjectOxidative stress-
dc.subject.meshCell Lineen_HK
dc.subject.meshCell Proliferationen_HK
dc.subject.meshDose-Response Relationship, Drugen_HK
dc.subject.meshEnzyme Activationen_HK
dc.subject.meshEstradiol - analogs & derivatives - pharmacologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMAP Kinase Signaling System - drug effectsen_HK
dc.subject.meshMitochondria - drug effects - metabolismen_HK
dc.subject.meshOxidative Stress - drug effectsen_HK
dc.subject.meshTubulin Modulators - pharmacologyen_HK
dc.title2-Methoxyestradiol induces endoreduplication through the induction of mitochondrial oxidative stress and the activation of MAPK signaling pathwaysen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-2952&volume=&spage=&epage=&date=2009&atitle=2-Methoxyestradiol+induces+endoreduplication+through+the+induction+of+mitochondrial+oxidative+stress+and+the+activation+of+MAPK+signaling+pathwaysen_HK
dc.identifier.emailWong, AS:awong1@hkucc.hku.hken_HK
dc.identifier.emailLung, HL:hllung2@hku.hken_HK
dc.identifier.emailLung, ML:mlilung@hku.hken_HK
dc.identifier.authorityWong, AS=rp00805en_HK
dc.identifier.authorityLung, HL=rp00299en_HK
dc.identifier.authorityLung, ML=rp00300en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.bcp.2009.10.018en_HK
dc.identifier.pmid19883629-
dc.identifier.scopuseid_2-s2.0-74149083977en_HK
dc.identifier.hkuros168360en_HK
dc.identifier.hkuros174120-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-74149083977&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume79en_HK
dc.identifier.issue6en_HK
dc.identifier.spage825en_HK
dc.identifier.epage841en_HK
dc.identifier.isiWOS:000274165500004-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectGinsenosides as functional ligands of steroid hormone receptors: from ligand-receptor interaction to cellular homeostasis-
dc.identifier.scopusauthoridTing, CM=24178752700en_HK
dc.identifier.scopusauthoridLee, YM=36990915600en_HK
dc.identifier.scopusauthoridWong, CKC=35276549400en_HK
dc.identifier.scopusauthoridWong, AS=23987963300en_HK
dc.identifier.scopusauthoridLung, HL=6603819904en_HK
dc.identifier.scopusauthoridLung, ML=7006411788en_HK
dc.identifier.scopusauthoridLo, KW=7402101603en_HK
dc.identifier.scopusauthoridWong, RNS=7402126957en_HK
dc.identifier.scopusauthoridMak, NK=35587830100en_HK
dc.identifier.citeulike6197735-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats