A biscarbene gold(I)-NHC-complex overcomes cisplatin-resistance in A2780 and W1 ovarian cancer cells highlighting pERK as regulator of apoptosis
Purpose Cisplatin resistance is the major obstacle in the clinical treatment of ovarian cancer patients. Molecular mechanisms of cisplatin resistance are multifaceted. Gold(I)-compounds, i.e. N -heterocyclic carbene-gold(I)-complexes (NHC-Au(I)) has been regarded as promising cytotoxic drug candidat...
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| Veröffentlicht in: | Cancer chemotherapy and pharmacology 2023-07, Vol.92 (1), p.57-69 |
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| creator | König, Philipp Zhulenko, Roman Suparman, Eloy Hoffmeister, Henrik Bückreiß, Nico Ott, Ingo Bendas, Gerd |
| description | Purpose
Cisplatin resistance is the major obstacle in the clinical treatment of ovarian cancer patients. Molecular mechanisms of cisplatin resistance are multifaceted. Gold(I)-compounds, i.e.
N
-heterocyclic carbene-gold(I)-complexes (NHC-Au(I)) has been regarded as promising cytotoxic drug candidates. However, their potential to overcome cisplatin resistance has hardly been addressed yet. Here we investigated the activity of the gold(I) drug auranofin and the NHC-Au(I)-compound MC3 in W1CR and A2780cis cisplatin-resistant ovarian cancer cells.
Methods
Cytotoxicity of auranofin and MC3 was detected by MTT assay, correlated with intracellular gold(I) content, analyzed by AAS, and with flow cytometric detection of the cell cycle. Insight into cellular redox balance was provided by fluorimetric ROS-formation assay and western blotting thioredoxin (Trx) and Nrf2. The role of ERK was elucidated by using the inhibitor SCH772984 and its impact on cytotoxicity upon co-treatment with cisplatin and Au(I)-compounds, respectively.
Results
MC3 overcomes cisplatin resistance in A2780cis and W1CR, and auranofin in W1CR cells completely, which is neither reflected by intracellular gold levels nor cell cycle changes. Upregulated redox balance appears as a basis for resistance. W1CR cells possess higher Trx levels, whereas A2780cis cells display strong Nrf2 expression as anti-oxidative protection. Nevertheless, overcoming redox balance appears not primary mode of activity comparing cisplatin and gold(I)-compounds. pERK emerges as a critical component and thus a promising target for overcoming resistance, regulating apoptosis differently in response to either gold(I) or cisplatin in A2780 cells.
Conclusion
These data reflect the complexity of cisplatin resistance in cell models and emphasize NHC-Au(I)-complexes as prospective cytotoxic agents for further investigations in that respect. |
| doi_str_mv | 10.1007/s00280-023-04548-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10261188</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3040458899</sourcerecordid><originalsourceid>FETCH-LOGICAL-c508t-61a66e1c3279ff8d9e6f3f107daf6181077f2839243bc6eb0a9b9e939e6a408d3</originalsourceid><addsrcrecordid>eNqFkk1v1DAQhi0EosvCH-CALHEpB8P4I7FzQqtVoRUVSAjE0XIcJ-sqawc7qeBf8JPxsqV8HOBgeaR55rVn5kXoMYXnFEC-yABMAQHGCYhKKELvoBUVnBFQgt9FK-BCkEqCOEEPcr4CAEE5v49OuGSSNZyt0LcNbn22JrUuODzEsTu9eEbenm-JjftpdF9wvHapxC5j6_M0mtkHklz2eTbBOuwD3jCpAJvQ4U-04CZ5E7A9ZBO2bhwz3vlhN5ZTagc8nb1_g03GyQ1LkYsJxx6bKU5zLKoP0b3ejNk9urnX6OOrsw_bc3L57vXFdnNJbAVqJjU1de2o5Uw2fa-6xtU97ynIzvQ1VSWQPVO8YYK3tnYtmKZtXMMLZwSojq_Ry6PutLR711kX5mRGPSW_N-mrjsbrPzPB7_QQrzUFVlOqVFE4vVFI8fPi8qz3ZZKlXxNcXLLmIMpalGqa_6JMMSZBVjUr6NO_0Ku4pFBGcaCqqha87HCN2JGyKeacXH_7cQr6YA59NIcu5tA_zKFpKXrye8u3JT_dUAB-BHJJhcGlX2__Q_Y7wV_E_A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2825564313</pqid></control><display><type>article</type><title>A biscarbene gold(I)-NHC-complex overcomes cisplatin-resistance in A2780 and W1 ovarian cancer cells highlighting pERK as regulator of apoptosis</title><source>MEDLINE</source><source>SpringerLink Journals</source><creator>König, Philipp ; Zhulenko, Roman ; Suparman, Eloy ; Hoffmeister, Henrik ; Bückreiß, Nico ; Ott, Ingo ; Bendas, Gerd</creator><creatorcontrib>König, Philipp ; Zhulenko, Roman ; Suparman, Eloy ; Hoffmeister, Henrik ; Bückreiß, Nico ; Ott, Ingo ; Bendas, Gerd</creatorcontrib><description>Purpose
Cisplatin resistance is the major obstacle in the clinical treatment of ovarian cancer patients. Molecular mechanisms of cisplatin resistance are multifaceted. Gold(I)-compounds, i.e.
N
-heterocyclic carbene-gold(I)-complexes (NHC-Au(I)) has been regarded as promising cytotoxic drug candidates. However, their potential to overcome cisplatin resistance has hardly been addressed yet. Here we investigated the activity of the gold(I) drug auranofin and the NHC-Au(I)-compound MC3 in W1CR and A2780cis cisplatin-resistant ovarian cancer cells.
Methods
Cytotoxicity of auranofin and MC3 was detected by MTT assay, correlated with intracellular gold(I) content, analyzed by AAS, and with flow cytometric detection of the cell cycle. Insight into cellular redox balance was provided by fluorimetric ROS-formation assay and western blotting thioredoxin (Trx) and Nrf2. The role of ERK was elucidated by using the inhibitor SCH772984 and its impact on cytotoxicity upon co-treatment with cisplatin and Au(I)-compounds, respectively.
Results
MC3 overcomes cisplatin resistance in A2780cis and W1CR, and auranofin in W1CR cells completely, which is neither reflected by intracellular gold levels nor cell cycle changes. Upregulated redox balance appears as a basis for resistance. W1CR cells possess higher Trx levels, whereas A2780cis cells display strong Nrf2 expression as anti-oxidative protection. Nevertheless, overcoming redox balance appears not primary mode of activity comparing cisplatin and gold(I)-compounds. pERK emerges as a critical component and thus a promising target for overcoming resistance, regulating apoptosis differently in response to either gold(I) or cisplatin in A2780 cells.
Conclusion
These data reflect the complexity of cisplatin resistance in cell models and emphasize NHC-Au(I)-complexes as prospective cytotoxic agents for further investigations in that respect.</description><identifier>ISSN: 0344-5704</identifier><identifier>EISSN: 1432-0843</identifier><identifier>DOI: 10.1007/s00280-023-04548-1</identifier><identifier>PMID: 37272932</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Antineoplastic Agents - pharmacology ; Apoptosis ; Auranofin - pharmacology ; Auranofin - therapeutic use ; Cancer ; Cancer Research ; Cell culture ; Cell cycle ; Cell Line, Tumor ; Cisplatin ; Cisplatin - pharmacology ; Critical components ; Cytotoxic agents ; Cytotoxicity ; Drug development ; Drug Resistance, Neoplasm ; Female ; Flow cytometry ; fluorometry ; Gold ; heterocyclic nitrogen compounds ; Humans ; Intracellular ; Medicine ; Medicine & Public Health ; Molecular modelling ; NF-E2-Related Factor 2 ; Oncology ; Original ; Original Article ; Ovarian cancer ; ovarian neoplasms ; Ovarian Neoplasms - drug therapy ; Pharmacology/Toxicology ; Prospective Studies ; Thioredoxin ; thioredoxins ; Toxicity ; toxicity testing ; Western blotting</subject><ispartof>Cancer chemotherapy and pharmacology, 2023-07, Vol.92 (1), p.57-69</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-61a66e1c3279ff8d9e6f3f107daf6181077f2839243bc6eb0a9b9e939e6a408d3</citedby><cites>FETCH-LOGICAL-c508t-61a66e1c3279ff8d9e6f3f107daf6181077f2839243bc6eb0a9b9e939e6a408d3</cites><orcidid>0000-0002-8667-7201</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00280-023-04548-1$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00280-023-04548-1$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37272932$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>König, Philipp</creatorcontrib><creatorcontrib>Zhulenko, Roman</creatorcontrib><creatorcontrib>Suparman, Eloy</creatorcontrib><creatorcontrib>Hoffmeister, Henrik</creatorcontrib><creatorcontrib>Bückreiß, Nico</creatorcontrib><creatorcontrib>Ott, Ingo</creatorcontrib><creatorcontrib>Bendas, Gerd</creatorcontrib><title>A biscarbene gold(I)-NHC-complex overcomes cisplatin-resistance in A2780 and W1 ovarian cancer cells highlighting pERK as regulator of apoptosis</title><title>Cancer chemotherapy and pharmacology</title><addtitle>Cancer Chemother Pharmacol</addtitle><addtitle>Cancer Chemother Pharmacol</addtitle><description>Purpose
Cisplatin resistance is the major obstacle in the clinical treatment of ovarian cancer patients. Molecular mechanisms of cisplatin resistance are multifaceted. Gold(I)-compounds, i.e.
N
-heterocyclic carbene-gold(I)-complexes (NHC-Au(I)) has been regarded as promising cytotoxic drug candidates. However, their potential to overcome cisplatin resistance has hardly been addressed yet. Here we investigated the activity of the gold(I) drug auranofin and the NHC-Au(I)-compound MC3 in W1CR and A2780cis cisplatin-resistant ovarian cancer cells.
Methods
Cytotoxicity of auranofin and MC3 was detected by MTT assay, correlated with intracellular gold(I) content, analyzed by AAS, and with flow cytometric detection of the cell cycle. Insight into cellular redox balance was provided by fluorimetric ROS-formation assay and western blotting thioredoxin (Trx) and Nrf2. The role of ERK was elucidated by using the inhibitor SCH772984 and its impact on cytotoxicity upon co-treatment with cisplatin and Au(I)-compounds, respectively.
Results
MC3 overcomes cisplatin resistance in A2780cis and W1CR, and auranofin in W1CR cells completely, which is neither reflected by intracellular gold levels nor cell cycle changes. Upregulated redox balance appears as a basis for resistance. W1CR cells possess higher Trx levels, whereas A2780cis cells display strong Nrf2 expression as anti-oxidative protection. Nevertheless, overcoming redox balance appears not primary mode of activity comparing cisplatin and gold(I)-compounds. pERK emerges as a critical component and thus a promising target for overcoming resistance, regulating apoptosis differently in response to either gold(I) or cisplatin in A2780 cells.
Conclusion
These data reflect the complexity of cisplatin resistance in cell models and emphasize NHC-Au(I)-complexes as prospective cytotoxic agents for further investigations in that respect.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Auranofin - pharmacology</subject><subject>Auranofin - therapeutic use</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Cisplatin</subject><subject>Cisplatin - pharmacology</subject><subject>Critical components</subject><subject>Cytotoxic agents</subject><subject>Cytotoxicity</subject><subject>Drug development</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>fluorometry</subject><subject>Gold</subject><subject>heterocyclic nitrogen compounds</subject><subject>Humans</subject><subject>Intracellular</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular modelling</subject><subject>NF-E2-Related Factor 2</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Ovarian cancer</subject><subject>ovarian neoplasms</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Pharmacology/Toxicology</subject><subject>Prospective Studies</subject><subject>Thioredoxin</subject><subject>thioredoxins</subject><subject>Toxicity</subject><subject>toxicity testing</subject><subject>Western blotting</subject><issn>0344-5704</issn><issn>1432-0843</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkk1v1DAQhi0EosvCH-CALHEpB8P4I7FzQqtVoRUVSAjE0XIcJ-sqawc7qeBf8JPxsqV8HOBgeaR55rVn5kXoMYXnFEC-yABMAQHGCYhKKELvoBUVnBFQgt9FK-BCkEqCOEEPcr4CAEE5v49OuGSSNZyt0LcNbn22JrUuODzEsTu9eEbenm-JjftpdF9wvHapxC5j6_M0mtkHklz2eTbBOuwD3jCpAJvQ4U-04CZ5E7A9ZBO2bhwz3vlhN5ZTagc8nb1_g03GyQ1LkYsJxx6bKU5zLKoP0b3ejNk9urnX6OOrsw_bc3L57vXFdnNJbAVqJjU1de2o5Uw2fa-6xtU97ynIzvQ1VSWQPVO8YYK3tnYtmKZtXMMLZwSojq_Ry6PutLR711kX5mRGPSW_N-mrjsbrPzPB7_QQrzUFVlOqVFE4vVFI8fPi8qz3ZZKlXxNcXLLmIMpalGqa_6JMMSZBVjUr6NO_0Ku4pFBGcaCqqha87HCN2JGyKeacXH_7cQr6YA59NIcu5tA_zKFpKXrye8u3JT_dUAB-BHJJhcGlX2__Q_Y7wV_E_A</recordid><startdate>20230701</startdate><enddate>20230701</enddate><creator>König, Philipp</creator><creator>Zhulenko, Roman</creator><creator>Suparman, Eloy</creator><creator>Hoffmeister, Henrik</creator><creator>Bückreiß, Nico</creator><creator>Ott, Ingo</creator><creator>Bendas, Gerd</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8667-7201</orcidid></search><sort><creationdate>20230701</creationdate><title>A biscarbene gold(I)-NHC-complex overcomes cisplatin-resistance in A2780 and W1 ovarian cancer cells highlighting pERK as regulator of apoptosis</title><author>König, Philipp ; Zhulenko, Roman ; Suparman, Eloy ; Hoffmeister, Henrik ; Bückreiß, Nico ; Ott, Ingo ; Bendas, Gerd</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c508t-61a66e1c3279ff8d9e6f3f107daf6181077f2839243bc6eb0a9b9e939e6a408d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Auranofin - pharmacology</topic><topic>Auranofin - therapeutic use</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Cell culture</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Cisplatin</topic><topic>Cisplatin - pharmacology</topic><topic>Critical components</topic><topic>Cytotoxic agents</topic><topic>Cytotoxicity</topic><topic>Drug development</topic><topic>Drug Resistance, Neoplasm</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>fluorometry</topic><topic>Gold</topic><topic>heterocyclic nitrogen compounds</topic><topic>Humans</topic><topic>Intracellular</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular modelling</topic><topic>NF-E2-Related Factor 2</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Ovarian cancer</topic><topic>ovarian neoplasms</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Pharmacology/Toxicology</topic><topic>Prospective Studies</topic><topic>Thioredoxin</topic><topic>thioredoxins</topic><topic>Toxicity</topic><topic>toxicity testing</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>König, Philipp</creatorcontrib><creatorcontrib>Zhulenko, Roman</creatorcontrib><creatorcontrib>Suparman, Eloy</creatorcontrib><creatorcontrib>Hoffmeister, Henrik</creatorcontrib><creatorcontrib>Bückreiß, Nico</creatorcontrib><creatorcontrib>Ott, Ingo</creatorcontrib><creatorcontrib>Bendas, Gerd</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer chemotherapy and pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>König, Philipp</au><au>Zhulenko, Roman</au><au>Suparman, Eloy</au><au>Hoffmeister, Henrik</au><au>Bückreiß, Nico</au><au>Ott, Ingo</au><au>Bendas, Gerd</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A biscarbene gold(I)-NHC-complex overcomes cisplatin-resistance in A2780 and W1 ovarian cancer cells highlighting pERK as regulator of apoptosis</atitle><jtitle>Cancer chemotherapy and pharmacology</jtitle><stitle>Cancer Chemother Pharmacol</stitle><addtitle>Cancer Chemother Pharmacol</addtitle><date>2023-07-01</date><risdate>2023</risdate><volume>92</volume><issue>1</issue><spage>57</spage><epage>69</epage><pages>57-69</pages><issn>0344-5704</issn><eissn>1432-0843</eissn><abstract>Purpose
Cisplatin resistance is the major obstacle in the clinical treatment of ovarian cancer patients. Molecular mechanisms of cisplatin resistance are multifaceted. Gold(I)-compounds, i.e.
N
-heterocyclic carbene-gold(I)-complexes (NHC-Au(I)) has been regarded as promising cytotoxic drug candidates. However, their potential to overcome cisplatin resistance has hardly been addressed yet. Here we investigated the activity of the gold(I) drug auranofin and the NHC-Au(I)-compound MC3 in W1CR and A2780cis cisplatin-resistant ovarian cancer cells.
Methods
Cytotoxicity of auranofin and MC3 was detected by MTT assay, correlated with intracellular gold(I) content, analyzed by AAS, and with flow cytometric detection of the cell cycle. Insight into cellular redox balance was provided by fluorimetric ROS-formation assay and western blotting thioredoxin (Trx) and Nrf2. The role of ERK was elucidated by using the inhibitor SCH772984 and its impact on cytotoxicity upon co-treatment with cisplatin and Au(I)-compounds, respectively.
Results
MC3 overcomes cisplatin resistance in A2780cis and W1CR, and auranofin in W1CR cells completely, which is neither reflected by intracellular gold levels nor cell cycle changes. Upregulated redox balance appears as a basis for resistance. W1CR cells possess higher Trx levels, whereas A2780cis cells display strong Nrf2 expression as anti-oxidative protection. Nevertheless, overcoming redox balance appears not primary mode of activity comparing cisplatin and gold(I)-compounds. pERK emerges as a critical component and thus a promising target for overcoming resistance, regulating apoptosis differently in response to either gold(I) or cisplatin in A2780 cells.
Conclusion
These data reflect the complexity of cisplatin resistance in cell models and emphasize NHC-Au(I)-complexes as prospective cytotoxic agents for further investigations in that respect.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>37272932</pmid><doi>10.1007/s00280-023-04548-1</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8667-7201</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antineoplastic Agents - pharmacology Apoptosis Auranofin - pharmacology Auranofin - therapeutic use Cancer Cancer Research Cell culture Cell cycle Cell Line, Tumor Cisplatin Cisplatin - pharmacology Critical components Cytotoxic agents Cytotoxicity Drug development Drug Resistance, Neoplasm Female Flow cytometry fluorometry Gold heterocyclic nitrogen compounds Humans Intracellular Medicine Medicine & Public Health Molecular modelling NF-E2-Related Factor 2 Oncology Original Original Article Ovarian cancer ovarian neoplasms Ovarian Neoplasms - drug therapy Pharmacology/Toxicology Prospective Studies Thioredoxin thioredoxins Toxicity toxicity testing Western blotting |
| title | A biscarbene gold(I)-NHC-complex overcomes cisplatin-resistance in A2780 and W1 ovarian cancer cells highlighting pERK as regulator of apoptosis |
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