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Article: Gold(III) complexes inhibit growth of cisplatin-resistant ovarian cancer in association with upregulation of proapoptotic PMS2 gene.

TitleGold(III) complexes inhibit growth of cisplatin-resistant ovarian cancer in association with upregulation of proapoptotic PMS2 gene.
Authors
Issue Date2014
PublisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/publishing/journals/sc/About.asp
Citation
Chemical Science, 2014, v. 5, p. 1579-1584 How to Cite?
AbstractVarious gold complexes have been known to overcome cisplatin resistance in cancer cells. Yet, their in vivo anti-tumor efficacies and detailed action mechanisms in overcoming this resistance remain largely unexplored. In this work we have established a xenograft model simultaneously consisting of both cisplatin-sensitive and cisplatin-resistant tumors by inoculating human ovarian cancer cells A2780 and its cisplatin-resistant variant A2780cis into different flanks of the same nude mouse. Towards this model, a gold(III) porphyrin complex [AuIII(TPP)]Cl (gold-1a, wherein [TPP]2- = meso-tetraphenylporphyrinato ligand) was found to effectively inhibit the growth of both kinds of tumors, while cisplatin failed to suppress the growth of A2780cis tumors under similar conditions. In both A2780 and A2780cis cells, gold-1a was found to transcriptionally upregulate postmeiotic segregation increased 2 (PMS2) which has DNA mismatch repair and proapoptotic functions. Suppression of PMS2 by RNA interference in A2780cis cells partially rescued the gold-1a-induced death of the cells, indicating that gold-1a inhibited growth of cisplatin-resistant ovarian cancer in association with upregulation of this gene. Two other stable gold(III) analogues including gold(III) octaethylporphyrin (2) and gold(III)-NHC (3) complexes also displayed similar anti-cancer activities on A2780cis cells and capability in PMS2 regulation. In contrast, a gold(I) phosphine complex (4), a gold(I) thiourea complex (5), the relatively less stable KAuIIICl4 and cisplatin all displayed a preferential cytotoxicity only towards the cisplatin-sensitive A2780 cells. Taken together, this work has demonstrated the prospect of gold(III) complexes for the treatment of cisplatin-resistant/ relapsed ovarian cancers.
Persistent Identifierhttp://hdl.handle.net/10722/198992
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLum, CTen_US
dc.contributor.authorSun, RWYen_US
dc.contributor.authorZOU, Ten_US
dc.contributor.authorChe, CMen_US
dc.date.accessioned2014-07-22T00:59:52Z-
dc.date.available2014-07-22T00:59:52Z-
dc.date.issued2014en_US
dc.identifier.citationChemical Science, 2014, v. 5, p. 1579-1584en_US
dc.identifier.urihttp://hdl.handle.net/10722/198992-
dc.description.abstractVarious gold complexes have been known to overcome cisplatin resistance in cancer cells. Yet, their in vivo anti-tumor efficacies and detailed action mechanisms in overcoming this resistance remain largely unexplored. In this work we have established a xenograft model simultaneously consisting of both cisplatin-sensitive and cisplatin-resistant tumors by inoculating human ovarian cancer cells A2780 and its cisplatin-resistant variant A2780cis into different flanks of the same nude mouse. Towards this model, a gold(III) porphyrin complex [AuIII(TPP)]Cl (gold-1a, wherein [TPP]2- = meso-tetraphenylporphyrinato ligand) was found to effectively inhibit the growth of both kinds of tumors, while cisplatin failed to suppress the growth of A2780cis tumors under similar conditions. In both A2780 and A2780cis cells, gold-1a was found to transcriptionally upregulate postmeiotic segregation increased 2 (PMS2) which has DNA mismatch repair and proapoptotic functions. Suppression of PMS2 by RNA interference in A2780cis cells partially rescued the gold-1a-induced death of the cells, indicating that gold-1a inhibited growth of cisplatin-resistant ovarian cancer in association with upregulation of this gene. Two other stable gold(III) analogues including gold(III) octaethylporphyrin (2) and gold(III)-NHC (3) complexes also displayed similar anti-cancer activities on A2780cis cells and capability in PMS2 regulation. In contrast, a gold(I) phosphine complex (4), a gold(I) thiourea complex (5), the relatively less stable KAuIIICl4 and cisplatin all displayed a preferential cytotoxicity only towards the cisplatin-sensitive A2780 cells. Taken together, this work has demonstrated the prospect of gold(III) complexes for the treatment of cisplatin-resistant/ relapsed ovarian cancers.en_US
dc.languageengen_US
dc.publisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/publishing/journals/sc/About.aspen_US
dc.relation.ispartofChemical Scienceen_US
dc.titleGold(III) complexes inhibit growth of cisplatin-resistant ovarian cancer in association with upregulation of proapoptotic PMS2 gene.en_US
dc.typeArticleen_US
dc.identifier.emailLum, CT: ctlum@graduate.hku.hken_US
dc.identifier.emailSun, RWY: rwysun@hku.hken_US
dc.identifier.emailChe, CM: cmche@hku.hken_US
dc.identifier.authorityLum, CT=rp00757en_US
dc.identifier.authoritySun, RWY=rp00781en_US
dc.identifier.authorityChe, CM=rp00670en_US
dc.identifier.doi10.1039/c3sc53203hen_US
dc.identifier.hkuros230884en_US
dc.identifier.volume5en_US
dc.identifier.spage1579en_US
dc.identifier.epage1584en_US
dc.identifier.isiWOS:000332467400041-

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