File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Role of STAT3/5 and Bcl-2/xL in 2-methoxyestradiol-induced endoreduplication of nasopharyngeal carcinoma cells

TitleRole of STAT3/5 and Bcl-2/xL in 2-methoxyestradiol-induced endoreduplication of nasopharyngeal carcinoma cells
Authors
Keywords2-Methoxyestradiol
Bcl-2/Xl
Endoreduplication
Nasopharyngeal Carcinoma
Stat3/5
Issue Date2012
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/
Citation
Molecular Carcinogenesis, 2012, v. 51 n. 12, p. 963-972 How to Cite?
Abstract
2-methoxyestradiol (2ME2), an endogenous metabolite of 17-β-estradiol, has been shown to induce apoptosis and cell cycle arrest in various tumor models. We have previously shown that 2ME2 induced endoreduplication in a well-differentiated nasopharyngeal carcinoma (NPC) HK-1 and a poorly differentiated C666-1 cell line. In the present study, we studied the survival factors involved in 2ME2-induced endoreduplicating NPC cells. In the HK-1 cells, knockdown of BcL-xL expression by siRNA resulted in the reduction of endoreduplication and an increase in the percentage of apoptosis. Further mechanistic study revealed that 2ME2 enhanced the expression of the phosphorylated form of STAT5 (p-STAT5-Y694), but not p-STAT3 (Y705) and p-STAT3 (S727), in the nucleus of HK-1 cells. Pre-treatment of cells with JAK/STAT inhibitor AG490 and STAT5 inhibitor resulted not only in the reduced expression of Bcl-xL, but also reduced the percentage of endoreduplicating cells. In contrast, 2ME2 enhanced the expression of p-STAT3 in the poorly differentiated C666-1 cells. Pharmacological inhibition of STAT3 or Bcl-2/xL resulted in a decrease in endoreduplication of C666-1 cells. Taken together, the expression of p-STAT5 and p-STAT3 was upregulated in 2ME2-induced endoreduplicating HK-1 and C666-1 cells, respectively. Combination of 2ME2 with Bcl-2/xL inhibitor is a novel strategy to reduce the formation of endoreduplicating cells during chemotherapeutic treatment of NPC. © 2011 Wiley Periodicals, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/149770
ISSN
2013 Impact Factor: 4.770
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTing, CMen_US
dc.contributor.authorWong, CKen_US
dc.contributor.authorWong, RNSen_US
dc.contributor.authorLo, KWen_US
dc.contributor.authorLee, AWen_US
dc.contributor.authorTsao, GSen_US
dc.contributor.authorLung, MLen_US
dc.contributor.authorMak, NKen_US
dc.date.accessioned2012-06-26T05:58:19Z-
dc.date.available2012-06-26T05:58:19Z-
dc.date.issued2012en_US
dc.identifier.citationMolecular Carcinogenesis, 2012, v. 51 n. 12, p. 963-972en_US
dc.identifier.issn0899-1987en_US
dc.identifier.urihttp://hdl.handle.net/10722/149770-
dc.description.abstract2-methoxyestradiol (2ME2), an endogenous metabolite of 17-β-estradiol, has been shown to induce apoptosis and cell cycle arrest in various tumor models. We have previously shown that 2ME2 induced endoreduplication in a well-differentiated nasopharyngeal carcinoma (NPC) HK-1 and a poorly differentiated C666-1 cell line. In the present study, we studied the survival factors involved in 2ME2-induced endoreduplicating NPC cells. In the HK-1 cells, knockdown of BcL-xL expression by siRNA resulted in the reduction of endoreduplication and an increase in the percentage of apoptosis. Further mechanistic study revealed that 2ME2 enhanced the expression of the phosphorylated form of STAT5 (p-STAT5-Y694), but not p-STAT3 (Y705) and p-STAT3 (S727), in the nucleus of HK-1 cells. Pre-treatment of cells with JAK/STAT inhibitor AG490 and STAT5 inhibitor resulted not only in the reduced expression of Bcl-xL, but also reduced the percentage of endoreduplicating cells. In contrast, 2ME2 enhanced the expression of p-STAT3 in the poorly differentiated C666-1 cells. Pharmacological inhibition of STAT3 or Bcl-2/xL resulted in a decrease in endoreduplication of C666-1 cells. Taken together, the expression of p-STAT5 and p-STAT3 was upregulated in 2ME2-induced endoreduplicating HK-1 and C666-1 cells, respectively. Combination of 2ME2 with Bcl-2/xL inhibitor is a novel strategy to reduce the formation of endoreduplicating cells during chemotherapeutic treatment of NPC. © 2011 Wiley Periodicals, Inc.en_US
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/en_US
dc.relation.ispartofMolecular Carcinogenesisen_US
dc.subject2-Methoxyestradiolen_US
dc.subjectBcl-2/Xlen_US
dc.subjectEndoreduplicationen_US
dc.subjectNasopharyngeal Carcinomaen_US
dc.subjectStat3/5en_US
dc.titleRole of STAT3/5 and Bcl-2/xL in 2-methoxyestradiol-induced endoreduplication of nasopharyngeal carcinoma cellsen_US
dc.typeArticleen_US
dc.identifier.emailTsao, GS:gswtsao@hkucc.hku.hken_US
dc.identifier.emailLung, ML:mlilung@hku.hken_US
dc.identifier.authorityTsao, GS=rp00399en_US
dc.identifier.authorityLung, ML=rp00300en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/mc.20867en_US
dc.identifier.pmid22006341-
dc.identifier.scopuseid_2-s2.0-84867743723en_US
dc.identifier.hkuros202589-
dc.identifier.isiWOS:000309922900005-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridTing, CM=24178752700en_US
dc.identifier.scopusauthoridWong, CK=7404954896en_US
dc.identifier.scopusauthoridWong, RNS=7402126957en_US
dc.identifier.scopusauthoridLo, KW=7402101603en_US
dc.identifier.scopusauthoridLee, AW=17035384900en_US
dc.identifier.scopusauthoridTsao, GS=7102813116en_US
dc.identifier.scopusauthoridLung, ML=7006411788en_US
dc.identifier.scopusauthoridMak, NK=36939018100en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats