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Article: Mechanisms of 2-methoxyestradiol-induced apoptosis and G2/M cell-cycle arrest of nasopharyngeal carcinoma cells

TitleMechanisms of 2-methoxyestradiol-induced apoptosis and G2/M cell-cycle arrest of nasopharyngeal carcinoma cells
Authors
Issue Date2008
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canlet
Citation
Cancer Letters, 2008, v. 268 n. 2, p. 295-307 How to Cite?
Abstract2-Methoxyestradiol (2ME2) is an endogenous metabolite of 17β-estradiol (E2). This study aims to examine the anti-tumour activities of 2ME2 on the poorly differentiated HONE-1 NPC cell line. At the concentration of 1 μM, 2ME2 was found to induce a short-term reversible G2/M cell-cycle arrest. Further 10-fold increase to 10 μM, 2ME2 induced both irreversible G2/M phase cell-cycle arrest and apoptosis. Induction of apoptosis and G2/M cell-cycle arrest was due to oxidative stress as both apoptosis and the proportion of cells arresting at G2/M phase could be reduced by the superoxide dismutase (SOD) mimetic, TEMPO. Induction of apoptosis was accompanied with proteolytic cleavage of caspase-9 and -3, but not caspase-8. Kinetics studies revealed that 2ME2 induced a time-dependent inhibition of extracellular signal-regulated protein kinase (ERK) and an activation of c-jun N-terminal kinases (JNKs). The chemical inhibitor of JNKs, SP600125, was found to reduce 2ME2-induced apoptosis of the HONE-1 cells. Confocal microscopy revealed that the induction of G2/M cell-cycle arrest was associated with the presence of immunoreactivity of p-cdc2 (Tyr15) in the nucleus. The G2/M cell-cycle arrest is also correlated with an increased level of inactive p-cdc25C (Ser216) in 2ME2-treated HONE-1 cells. Results from this study indicate that production of superoxide anions might be involved in 2ME2-induced apoptosis and G2/M cell-cycle arrest of the HONE-1 cells. © 2008 Elsevier Ireland Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/150823
ISSN
2015 Impact Factor: 5.992
2015 SCImago Journal Rankings: 2.331
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Baptist UniversityFSRS/05-06/01
Funding Information:

This work was supported by the Strategic Faculty Development Grant (FSRS/05-06/01) of Hong Kong Baptist University.

References

 

DC FieldValueLanguage
dc.contributor.authorLee, YMen_US
dc.contributor.authorTing, CMen_US
dc.contributor.authorCheng, YKen_US
dc.contributor.authorFan, TPen_US
dc.contributor.authorWong, RNSen_US
dc.contributor.authorLung, MLen_US
dc.contributor.authorMak, NKen_US
dc.date.accessioned2012-06-26T06:11:29Z-
dc.date.available2012-06-26T06:11:29Z-
dc.date.issued2008en_US
dc.identifier.citationCancer Letters, 2008, v. 268 n. 2, p. 295-307en_US
dc.identifier.issn0304-3835en_US
dc.identifier.urihttp://hdl.handle.net/10722/150823-
dc.description.abstract2-Methoxyestradiol (2ME2) is an endogenous metabolite of 17β-estradiol (E2). This study aims to examine the anti-tumour activities of 2ME2 on the poorly differentiated HONE-1 NPC cell line. At the concentration of 1 μM, 2ME2 was found to induce a short-term reversible G2/M cell-cycle arrest. Further 10-fold increase to 10 μM, 2ME2 induced both irreversible G2/M phase cell-cycle arrest and apoptosis. Induction of apoptosis and G2/M cell-cycle arrest was due to oxidative stress as both apoptosis and the proportion of cells arresting at G2/M phase could be reduced by the superoxide dismutase (SOD) mimetic, TEMPO. Induction of apoptosis was accompanied with proteolytic cleavage of caspase-9 and -3, but not caspase-8. Kinetics studies revealed that 2ME2 induced a time-dependent inhibition of extracellular signal-regulated protein kinase (ERK) and an activation of c-jun N-terminal kinases (JNKs). The chemical inhibitor of JNKs, SP600125, was found to reduce 2ME2-induced apoptosis of the HONE-1 cells. Confocal microscopy revealed that the induction of G2/M cell-cycle arrest was associated with the presence of immunoreactivity of p-cdc2 (Tyr15) in the nucleus. The G2/M cell-cycle arrest is also correlated with an increased level of inactive p-cdc25C (Ser216) in 2ME2-treated HONE-1 cells. Results from this study indicate that production of superoxide anions might be involved in 2ME2-induced apoptosis and G2/M cell-cycle arrest of the HONE-1 cells. © 2008 Elsevier Ireland Ltd. All rights reserved.en_US
dc.languageengen_US
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/canleten_US
dc.relation.ispartofCancer Lettersen_US
dc.subject.meshAntineoplastic Agents - Pharmacologyen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCell Division - Drug Effectsen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Proliferation - Drug Effectsen_US
dc.subject.meshEstradiol - Analogs & Derivatives - Pharmacologyen_US
dc.subject.meshFlow Cytometryen_US
dc.subject.meshG2 Phase - Drug Effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshJnk Mitogen-Activated Protein Kinases - Metabolismen_US
dc.subject.meshMap Kinase Signaling System - Drug Effectsen_US
dc.subject.meshNasopharyngeal Neoplasms - Drug Therapy - Pathologyen_US
dc.subject.meshOxidative Stressen_US
dc.subject.meshSuperoxide Dismutase - Physiologyen_US
dc.titleMechanisms of 2-methoxyestradiol-induced apoptosis and G2/M cell-cycle arrest of nasopharyngeal carcinoma cellsen_US
dc.typeArticleen_US
dc.identifier.emailLung, ML:mlilung@hku.hken_US
dc.identifier.authorityLung, ML=rp00300en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.canlet.2008.04.010en_US
dc.identifier.pmid18492602-
dc.identifier.scopuseid_2-s2.0-48549092524en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-48549092524&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume268en_US
dc.identifier.issue2en_US
dc.identifier.spage295en_US
dc.identifier.epage307en_US
dc.identifier.isiWOS:000259898500013-
dc.publisher.placeIrelanden_US
dc.identifier.scopusauthoridLee, YM=8521465600en_US
dc.identifier.scopusauthoridTing, CM=24178752700en_US
dc.identifier.scopusauthoridCheng, YK=9133925600en_US
dc.identifier.scopusauthoridFan, TP=36831423500en_US
dc.identifier.scopusauthoridWong, RNS=7402126957en_US
dc.identifier.scopusauthoridLung, ML=7006411788en_US
dc.identifier.scopusauthoridMak, NK=35582657000en_US

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