The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)‐Phenanthroline Complexes
Mononuclear copper(II)‐phenanthroline complexes have been widely investigated as anticancer agents whereas multinuclear copper(II)‐phenanthroline complexes are underexplored. Here the synthesis and characterisation of two new binuclear copper(II)‐phenanthroline complexes 1 and 2 is reported, compris...
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| Veröffentlicht in: | Chemistry : a European journal 2023-08, Vol.29 (45), p.e202301188-n/a |
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| creator | Osei, Priscilla B. Northcote‐Smith, Joshua Fang, Jiaxin Singh, Kuldip Ortu, Fabrizio Suntharalingam, Kogularamanan |
| description | Mononuclear copper(II)‐phenanthroline complexes have been widely investigated as anticancer agents whereas multinuclear copper(II)‐phenanthroline complexes are underexplored. Here the synthesis and characterisation of two new binuclear copper(II)‐phenanthroline complexes 1 and 2 is reported, comprising of 2,9‐dimethyl‐1,10‐phenanthroline or 2,9‐dimethyl‐4,7‐diphenyl‐1,10‐phenanthroline, terminal chloride ligands, and bridging chloride or hydroxide ligands. The binuclear copper(II) complex containing 2,9‐dimethyl‐1,10‐phenanthroline 1 displays nanomolar toxicity towards bulk breast cancer cells and breast cancer stem cells (CSCs) grown in monolayers, >50‐fold greater than cisplatin (an anticancer metallodrug) and salinomycin (a gold‐standard anti‐CSC agent). Spectacularly, 1 exhibits >100‐fold greater potency toward three‐dimensionally cultured mammospheres than cisplatin and salinomycin. Mechanistic studies show that 1 evokes breast CSC apoptosis by elevating intracellular reactive oxygen species levels and damaging genomic DNA (possibly by an oxidative mechanism). To the best of our knowledge, this is the first study to probe the anti‐breast CSC properties of binuclear copper(II)‐phenanthroline complexes.
Investigations of the anti‐cancer stem cell (CSC) properties of multinuclear metal complexes are rare. Here the synthesis, characterisation, and bulk breast cancer cell and breast CSC activity of two new binuclear copper(II) complexes are reported. The mechanism of action of the most stable and potent binuclear copper(II) complex were elucidated. |
| doi_str_mv | 10.1002/chem.202301188 |
| format | Article |
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Investigations of the anti‐cancer stem cell (CSC) properties of multinuclear metal complexes are rare. Here the synthesis, characterisation, and bulk breast cancer cell and breast CSC activity of two new binuclear copper(II) complexes are reported. The mechanism of action of the most stable and potent binuclear copper(II) complex were elucidated.</description><identifier>ISSN: 0947-6539</identifier><identifier>EISSN: 1521-3765</identifier><identifier>DOI: 10.1002/chem.202301188</identifier><identifier>PMID: 37249243</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Anticancer properties ; Antineoplastic Agents - pharmacology ; Antitumor agents ; antitumour agent ; Apoptosis ; artificial metallonuclease ; bioinorganic chemistry ; Breast cancer ; Breast Neoplasms - drug therapy ; cancer stem cell ; Cell Line, Tumor ; Chemistry ; Chlorides ; Cisplatin ; Coordination Complexes - pharmacology ; Copper ; DNA damage ; Female ; Humans ; Ligands ; Neoplastic Stem Cells ; Phenanthrolines - pharmacology ; Reactive oxygen species ; Salinomycin ; Stem cells ; Toxicity</subject><ispartof>Chemistry : a European journal, 2023-08, Vol.29 (45), p.e202301188-n/a</ispartof><rights>2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH</rights><rights>2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.</rights><rights>2023. This article 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-c4698-1d3195a861baed5a67312695ae835d680f6f1631ef60d4afe85c45934c510b623</citedby><cites>FETCH-LOGICAL-c4698-1d3195a861baed5a67312695ae835d680f6f1631ef60d4afe85c45934c510b623</cites><orcidid>0000-0002-7047-6384</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fchem.202301188$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fchem.202301188$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37249243$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Osei, Priscilla B.</creatorcontrib><creatorcontrib>Northcote‐Smith, Joshua</creatorcontrib><creatorcontrib>Fang, Jiaxin</creatorcontrib><creatorcontrib>Singh, Kuldip</creatorcontrib><creatorcontrib>Ortu, Fabrizio</creatorcontrib><creatorcontrib>Suntharalingam, Kogularamanan</creatorcontrib><title>The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)‐Phenanthroline Complexes</title><title>Chemistry : a European journal</title><addtitle>Chemistry</addtitle><description>Mononuclear copper(II)‐phenanthroline complexes have been widely investigated as anticancer agents whereas multinuclear copper(II)‐phenanthroline complexes are underexplored. Here the synthesis and characterisation of two new binuclear copper(II)‐phenanthroline complexes 1 and 2 is reported, comprising of 2,9‐dimethyl‐1,10‐phenanthroline or 2,9‐dimethyl‐4,7‐diphenyl‐1,10‐phenanthroline, terminal chloride ligands, and bridging chloride or hydroxide ligands. The binuclear copper(II) complex containing 2,9‐dimethyl‐1,10‐phenanthroline 1 displays nanomolar toxicity towards bulk breast cancer cells and breast cancer stem cells (CSCs) grown in monolayers, >50‐fold greater than cisplatin (an anticancer metallodrug) and salinomycin (a gold‐standard anti‐CSC agent). Spectacularly, 1 exhibits >100‐fold greater potency toward three‐dimensionally cultured mammospheres than cisplatin and salinomycin. Mechanistic studies show that 1 evokes breast CSC apoptosis by elevating intracellular reactive oxygen species levels and damaging genomic DNA (possibly by an oxidative mechanism). To the best of our knowledge, this is the first study to probe the anti‐breast CSC properties of binuclear copper(II)‐phenanthroline complexes.
Investigations of the anti‐cancer stem cell (CSC) properties of multinuclear metal complexes are rare. Here the synthesis, characterisation, and bulk breast cancer cell and breast CSC activity of two new binuclear copper(II) complexes are reported. The mechanism of action of the most stable and potent binuclear copper(II) complex were elucidated.</description><subject>Anticancer properties</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antitumor agents</subject><subject>antitumour agent</subject><subject>Apoptosis</subject><subject>artificial metallonuclease</subject><subject>bioinorganic chemistry</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>cancer stem cell</subject><subject>Cell Line, Tumor</subject><subject>Chemistry</subject><subject>Chlorides</subject><subject>Cisplatin</subject><subject>Coordination Complexes - pharmacology</subject><subject>Copper</subject><subject>DNA damage</subject><subject>Female</subject><subject>Humans</subject><subject>Ligands</subject><subject>Neoplastic Stem Cells</subject><subject>Phenanthrolines - pharmacology</subject><subject>Reactive oxygen species</subject><subject>Salinomycin</subject><subject>Stem cells</subject><subject>Toxicity</subject><issn>0947-6539</issn><issn>1521-3765</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS0EotPCliWKxKYsMvgn8dgr1IlKO1IrkChry-PcEJfEDnZSmF0fgWfsk-DRtAN0w8rSPd898rkHoVcEzwnG9J1poZ9TTBkmRIgnaEZKSnK24OVTNMOyWOS8ZPIAHcZ4jTGWnLHn6IAtaCFpwWYoXrWQLafuW7YMoOOYVdoZCFkFXZdpVz8afx6h32knZrQ3dtxkvsmW1k2mA53W_DBAOF6t3t7d_vrUgtNubIPvrIOk9UMHPyG-QM8a3UV4ef8eoS8fTq-q8_zi49mqOrnITcGlyEnNiCy14GStoS41XzBCeZqAYGXNBW54Qzgj0HBcF7oBUZqilKwwJcFrTtkRer_zHaZ1D7UBNwbdqSHYXoeN8tqqfxVnW_XV3yiyPRzhJDkc3zsE_32COKreRpPiawd-iooKmk4qCiET-uYReu2n4FK-RBWCpI7k1nC-o0zwMQZo9r8hWG0LVdtC1b7QtPD67wx7_KHBBMgd8MN2sPmPnarOTy__mP8G28GtQg</recordid><startdate>20230810</startdate><enddate>20230810</enddate><creator>Osei, Priscilla B.</creator><creator>Northcote‐Smith, Joshua</creator><creator>Fang, Jiaxin</creator><creator>Singh, Kuldip</creator><creator>Ortu, Fabrizio</creator><creator>Suntharalingam, Kogularamanan</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7047-6384</orcidid></search><sort><creationdate>20230810</creationdate><title>The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)‐Phenanthroline Complexes</title><author>Osei, Priscilla B. ; Northcote‐Smith, Joshua ; Fang, Jiaxin ; Singh, Kuldip ; Ortu, Fabrizio ; Suntharalingam, Kogularamanan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4698-1d3195a861baed5a67312695ae835d680f6f1631ef60d4afe85c45934c510b623</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Anticancer properties</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antitumor agents</topic><topic>antitumour agent</topic><topic>Apoptosis</topic><topic>artificial metallonuclease</topic><topic>bioinorganic chemistry</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>cancer stem cell</topic><topic>Cell Line, Tumor</topic><topic>Chemistry</topic><topic>Chlorides</topic><topic>Cisplatin</topic><topic>Coordination Complexes - pharmacology</topic><topic>Copper</topic><topic>DNA damage</topic><topic>Female</topic><topic>Humans</topic><topic>Ligands</topic><topic>Neoplastic Stem Cells</topic><topic>Phenanthrolines - pharmacology</topic><topic>Reactive oxygen species</topic><topic>Salinomycin</topic><topic>Stem cells</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Osei, Priscilla B.</creatorcontrib><creatorcontrib>Northcote‐Smith, Joshua</creatorcontrib><creatorcontrib>Fang, Jiaxin</creatorcontrib><creatorcontrib>Singh, Kuldip</creatorcontrib><creatorcontrib>Ortu, Fabrizio</creatorcontrib><creatorcontrib>Suntharalingam, Kogularamanan</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemistry : a European journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Osei, Priscilla B.</au><au>Northcote‐Smith, Joshua</au><au>Fang, Jiaxin</au><au>Singh, Kuldip</au><au>Ortu, Fabrizio</au><au>Suntharalingam, Kogularamanan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)‐Phenanthroline Complexes</atitle><jtitle>Chemistry : a European journal</jtitle><addtitle>Chemistry</addtitle><date>2023-08-10</date><risdate>2023</risdate><volume>29</volume><issue>45</issue><spage>e202301188</spage><epage>n/a</epage><pages>e202301188-n/a</pages><issn>0947-6539</issn><eissn>1521-3765</eissn><abstract>Mononuclear copper(II)‐phenanthroline complexes have been widely investigated as anticancer agents whereas multinuclear copper(II)‐phenanthroline complexes are underexplored. Here the synthesis and characterisation of two new binuclear copper(II)‐phenanthroline complexes 1 and 2 is reported, comprising of 2,9‐dimethyl‐1,10‐phenanthroline or 2,9‐dimethyl‐4,7‐diphenyl‐1,10‐phenanthroline, terminal chloride ligands, and bridging chloride or hydroxide ligands. The binuclear copper(II) complex containing 2,9‐dimethyl‐1,10‐phenanthroline 1 displays nanomolar toxicity towards bulk breast cancer cells and breast cancer stem cells (CSCs) grown in monolayers, >50‐fold greater than cisplatin (an anticancer metallodrug) and salinomycin (a gold‐standard anti‐CSC agent). Spectacularly, 1 exhibits >100‐fold greater potency toward three‐dimensionally cultured mammospheres than cisplatin and salinomycin. Mechanistic studies show that 1 evokes breast CSC apoptosis by elevating intracellular reactive oxygen species levels and damaging genomic DNA (possibly by an oxidative mechanism). To the best of our knowledge, this is the first study to probe the anti‐breast CSC properties of binuclear copper(II)‐phenanthroline complexes.
Investigations of the anti‐cancer stem cell (CSC) properties of multinuclear metal complexes are rare. Here the synthesis, characterisation, and bulk breast cancer cell and breast CSC activity of two new binuclear copper(II) complexes are reported. The mechanism of action of the most stable and potent binuclear copper(II) complex were elucidated.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37249243</pmid><doi>10.1002/chem.202301188</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-7047-6384</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Anticancer properties Antineoplastic Agents - pharmacology Antitumor agents antitumour agent Apoptosis artificial metallonuclease bioinorganic chemistry Breast cancer Breast Neoplasms - drug therapy cancer stem cell Cell Line, Tumor Chemistry Chlorides Cisplatin Coordination Complexes - pharmacology Copper DNA damage Female Humans Ligands Neoplastic Stem Cells Phenanthrolines - pharmacology Reactive oxygen species Salinomycin Stem cells Toxicity |
| title | The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)‐Phenanthroline Complexes |
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