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Article: Role of STAT3/5 and Bcl-2/xL in 2-methoxyestradiol-induced endoreduplication of nasopharyngeal carcinoma cells
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TitleRole of STAT3/5 and Bcl-2/xL in 2-methoxyestradiol-induced endoreduplication of nasopharyngeal carcinoma cells
 
AuthorsTing, CM2
Wong, CK2
Wong, RNS2
Lo, KW4
Lee, AW3
Tsao, GS1
Lung, ML1
Mak, NK2
 
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/
 
CitationMolecular Carcinogenesis, 2012, v. 51 n. 12, p. 963-972 [How to Cite?]
DOI: http://dx.doi.org/10.1002/mc.20867
 
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.
 
ISSN0899-1987
2012 Impact Factor: 4.269
2012 SCImago Journal Rankings: 1.235
 
DOIhttp://dx.doi.org/10.1002/mc.20867
 
DC FieldValue
dc.contributor.authorTing, CM
 
dc.contributor.authorWong, CK
 
dc.contributor.authorWong, RNS
 
dc.contributor.authorLo, KW
 
dc.contributor.authorLee, AW
 
dc.contributor.authorTsao, GS
 
dc.contributor.authorLung, ML
 
dc.contributor.authorMak, NK
 
dc.date.accessioned2012-06-26T05:58:19Z
 
dc.date.available2012-06-26T05:58:19Z
 
dc.date.issued2012
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationMolecular Carcinogenesis, 2012, v. 51 n. 12, p. 963-972 [How to Cite?]
DOI: http://dx.doi.org/10.1002/mc.20867
 
dc.identifier.doihttp://dx.doi.org/10.1002/mc.20867
 
dc.identifier.hkuros202589
 
dc.identifier.issn0899-1987
2012 Impact Factor: 4.269
2012 SCImago Journal Rankings: 1.235
 
dc.identifier.pmid22006341
 
dc.identifier.scopuseid_2-s2.0-84867743723
 
dc.identifier.urihttp://hdl.handle.net/10722/149770
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www.interscience.wiley.com/jpages/0899-1987/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofMolecular Carcinogenesis
 
dc.subject2-Methoxyestradiol
 
dc.subjectBcl-2/Xl
 
dc.subjectEndoreduplication
 
dc.subjectNasopharyngeal Carcinoma
 
dc.subjectStat3/5
 
dc.titleRole of STAT3/5 and Bcl-2/xL in 2-methoxyestradiol-induced endoreduplication of nasopharyngeal carcinoma cells
 
dc.typeArticle
 
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<contributor.author>Wong, CK</contributor.author>
<contributor.author>Wong, RNS</contributor.author>
<contributor.author>Lo, KW</contributor.author>
<contributor.author>Lee, AW</contributor.author>
<contributor.author>Tsao, GS</contributor.author>
<contributor.author>Lung, ML</contributor.author>
<contributor.author>Mak, NK</contributor.author>
<date.accessioned>2012-06-26T05:58:19Z</date.accessioned>
<date.available>2012-06-26T05:58:19Z</date.available>
<date.issued>2012</date.issued>
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<description.abstract>2-methoxyestradiol (2ME2), an endogenous metabolite of 17-&#946;-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. &#169; 2011 Wiley Periodicals, Inc.</description.abstract>
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<subject>2-Methoxyestradiol</subject>
<subject>Bcl-2/Xl</subject>
<subject>Endoreduplication</subject>
<subject>Nasopharyngeal Carcinoma</subject>
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<title>Role of STAT3/5 and Bcl-2/xL in 2-methoxyestradiol-induced endoreduplication of nasopharyngeal carcinoma cells</title>
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Author Affiliations
  1. The University of Hong Kong
  2. Hong Kong Baptist University
  3. Pamela Youde Nethersole Eastern Hospital
  4. Chinese University of Hong Kong