Manganese(ii) complexes stimulate antitumor immunity via aggravating DNA damage and activating the cGAS-STING pathway
Activating the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a promising immunotherapeutic strategy for cancer treatment. Manganese(ii) complexes MnPC and MnPVA (P = 1,10-phenanthroline, C = chlorine, and VA = valproic acid) were found to activate the cGAS-STING p...
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| Veröffentlicht in: | Chemical science (Cambridge) 2023-04, Vol.14 (16), p.4375-4389 |
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| creator | Cai, Linxiang Wang, Ying Chen, Yayu Chen, Hanhua Yang, Tao Zhang, Shuren Guo, Zijian Wang, Xiaoyong |
| description | Activating the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a promising immunotherapeutic strategy for cancer treatment. Manganese(ii) complexes MnPC and MnPVA (P = 1,10-phenanthroline, C = chlorine, and VA = valproic acid) were found to activate the cGAS-STING pathway. The complexes not only damaged DNA, but also inhibited histone deacetylases (HDACs) and poly adenosine diphosphate-ribose polymerase (PARP) to impede the repair of DNA damage, thereby promoting the leakage of DNA fragments into cytoplasm. The DNA fragments activated the cGAS-STING pathway, which initiated an innate immune response and a two-way communication between tumor cells and neighboring immune cells. The activated cGAS-STING further increased the production of type I interferons and secretion of pro-inflammatory cytokines (TNF-α and IL-6), boosting the tumor infiltration of dendritic cells and macrophages, as well as stimulating cytotoxic T cells to kill cancer cells
and
. Owing to the enhanced DNA-damaging ability, MnPC and MnPVA showed more potent immunocompetence and antitumor activity than Mn
ions, thus demonstrating great potential as chemoimmunotherapeutic agents for cancer treatment. |
| doi_str_mv | 10.1039/d2sc06036a |
| format | Article |
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and
. Owing to the enhanced DNA-damaging ability, MnPC and MnPVA showed more potent immunocompetence and antitumor activity than Mn
ions, thus demonstrating great potential as chemoimmunotherapeutic agents for cancer treatment.</description><identifier>ISSN: 2041-6520</identifier><identifier>EISSN: 2041-6539</identifier><identifier>DOI: 10.1039/d2sc06036a</identifier><identifier>PMID: 37123182</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Adenosine diphosphate ; Anticancer properties ; Cancer ; Cancer therapies ; Chemistry ; Chlorine ; Cytoplasm ; Damage ; Deoxyribonucleic acid ; DNA ; DNA damage ; Fragments ; Immune system ; Lymphocytes ; Macrophages ; Manganese ions ; Ribose ; Stimulators</subject><ispartof>Chemical science (Cambridge), 2023-04, Vol.14 (16), p.4375-4389</ispartof><rights>This journal is © The Royal Society of Chemistry.</rights><rights>Copyright Royal Society of Chemistry 2023</rights><rights>This journal is © The Royal Society of Chemistry 2023 The Royal Society of Chemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c407t-69a4a6dfd7a6d04da0504de7c7c39521123d8ddd19941a810b936ca6c83bd4be3</citedby><cites>FETCH-LOGICAL-c407t-69a4a6dfd7a6d04da0504de7c7c39521123d8ddd19941a810b936ca6c83bd4be3</cites><orcidid>0000-0003-4986-9308 ; 0000-0002-8338-9773</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132258/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10132258/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37123182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Linxiang</creatorcontrib><creatorcontrib>Wang, Ying</creatorcontrib><creatorcontrib>Chen, Yayu</creatorcontrib><creatorcontrib>Chen, Hanhua</creatorcontrib><creatorcontrib>Yang, Tao</creatorcontrib><creatorcontrib>Zhang, Shuren</creatorcontrib><creatorcontrib>Guo, Zijian</creatorcontrib><creatorcontrib>Wang, Xiaoyong</creatorcontrib><title>Manganese(ii) complexes stimulate antitumor immunity via aggravating DNA damage and activating the cGAS-STING pathway</title><title>Chemical science (Cambridge)</title><addtitle>Chem Sci</addtitle><description>Activating the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a promising immunotherapeutic strategy for cancer treatment. Manganese(ii) complexes MnPC and MnPVA (P = 1,10-phenanthroline, C = chlorine, and VA = valproic acid) were found to activate the cGAS-STING pathway. The complexes not only damaged DNA, but also inhibited histone deacetylases (HDACs) and poly adenosine diphosphate-ribose polymerase (PARP) to impede the repair of DNA damage, thereby promoting the leakage of DNA fragments into cytoplasm. The DNA fragments activated the cGAS-STING pathway, which initiated an innate immune response and a two-way communication between tumor cells and neighboring immune cells. The activated cGAS-STING further increased the production of type I interferons and secretion of pro-inflammatory cytokines (TNF-α and IL-6), boosting the tumor infiltration of dendritic cells and macrophages, as well as stimulating cytotoxic T cells to kill cancer cells
and
. Owing to the enhanced DNA-damaging ability, MnPC and MnPVA showed more potent immunocompetence and antitumor activity than Mn
ions, thus demonstrating great potential as chemoimmunotherapeutic agents for cancer treatment.</description><subject>Adenosine diphosphate</subject><subject>Anticancer properties</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Chemistry</subject><subject>Chlorine</subject><subject>Cytoplasm</subject><subject>Damage</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>Fragments</subject><subject>Immune system</subject><subject>Lymphocytes</subject><subject>Macrophages</subject><subject>Manganese ions</subject><subject>Ribose</subject><subject>Stimulators</subject><issn>2041-6520</issn><issn>2041-6539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNpdkU1rGzEQhkVpSIybS35AEfSSBrbRx36eirEbx-C4B6dnMZbktcJq15W0bv3vIyeOaTqHmYF5eJmZF6ErSr5RwqtbxbwkOeE5fEADRlKa5BmvPp56Ri7QpfdPJAbnNGPFObrgBWWclmyA-gdoa2i119fGfMWys9tG_9Ue-2Bs30DQGNpgQm87h421fWvCHu8MYKhrBzsIpq3xZDHCCizUB1phkMEcJ2GjsZyOlsnycbaY4i2EzR_Yf0Jna2i8vjzWIfp19-NxfJ_Mf05n49E8kSkpQpJXkEKu1qqImaQKSBazLmQheZUxGo9QpVKKVlVKoaRkVfFcQi5LvlLpSvMh-v6qu-1XViup2-CgEVtnLLi96MCI95PWbETd7QQllDOWlVHh-qjgut-99kFY46VumvizrveClaRklJOURfTLf-hT17s23negsirLKMkjdfNKSdd57_T6tA0l4uComLDl-MXRUYQ__7v_CX3zjz8DP2-cfA</recordid><startdate>20230426</startdate><enddate>20230426</enddate><creator>Cai, Linxiang</creator><creator>Wang, Ying</creator><creator>Chen, Yayu</creator><creator>Chen, Hanhua</creator><creator>Yang, Tao</creator><creator>Zhang, Shuren</creator><creator>Guo, Zijian</creator><creator>Wang, Xiaoyong</creator><general>Royal Society of Chemistry</general><general>The Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4986-9308</orcidid><orcidid>https://orcid.org/0000-0002-8338-9773</orcidid></search><sort><creationdate>20230426</creationdate><title>Manganese(ii) complexes stimulate antitumor immunity via aggravating DNA damage and activating the cGAS-STING pathway</title><author>Cai, Linxiang ; Wang, Ying ; Chen, Yayu ; Chen, Hanhua ; Yang, Tao ; Zhang, Shuren ; Guo, Zijian ; Wang, Xiaoyong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c407t-69a4a6dfd7a6d04da0504de7c7c39521123d8ddd19941a810b936ca6c83bd4be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adenosine diphosphate</topic><topic>Anticancer properties</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Chemistry</topic><topic>Chlorine</topic><topic>Cytoplasm</topic><topic>Damage</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA damage</topic><topic>Fragments</topic><topic>Immune system</topic><topic>Lymphocytes</topic><topic>Macrophages</topic><topic>Manganese ions</topic><topic>Ribose</topic><topic>Stimulators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cai, Linxiang</creatorcontrib><creatorcontrib>Wang, Ying</creatorcontrib><creatorcontrib>Chen, Yayu</creatorcontrib><creatorcontrib>Chen, Hanhua</creatorcontrib><creatorcontrib>Yang, Tao</creatorcontrib><creatorcontrib>Zhang, Shuren</creatorcontrib><creatorcontrib>Guo, Zijian</creatorcontrib><creatorcontrib>Wang, Xiaoyong</creatorcontrib><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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemical science (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cai, Linxiang</au><au>Wang, Ying</au><au>Chen, Yayu</au><au>Chen, Hanhua</au><au>Yang, Tao</au><au>Zhang, Shuren</au><au>Guo, Zijian</au><au>Wang, Xiaoyong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Manganese(ii) complexes stimulate antitumor immunity via aggravating DNA damage and activating the cGAS-STING pathway</atitle><jtitle>Chemical science (Cambridge)</jtitle><addtitle>Chem Sci</addtitle><date>2023-04-26</date><risdate>2023</risdate><volume>14</volume><issue>16</issue><spage>4375</spage><epage>4389</epage><pages>4375-4389</pages><issn>2041-6520</issn><eissn>2041-6539</eissn><abstract>Activating the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a promising immunotherapeutic strategy for cancer treatment. Manganese(ii) complexes MnPC and MnPVA (P = 1,10-phenanthroline, C = chlorine, and VA = valproic acid) were found to activate the cGAS-STING pathway. The complexes not only damaged DNA, but also inhibited histone deacetylases (HDACs) and poly adenosine diphosphate-ribose polymerase (PARP) to impede the repair of DNA damage, thereby promoting the leakage of DNA fragments into cytoplasm. The DNA fragments activated the cGAS-STING pathway, which initiated an innate immune response and a two-way communication between tumor cells and neighboring immune cells. The activated cGAS-STING further increased the production of type I interferons and secretion of pro-inflammatory cytokines (TNF-α and IL-6), boosting the tumor infiltration of dendritic cells and macrophages, as well as stimulating cytotoxic T cells to kill cancer cells
and
. Owing to the enhanced DNA-damaging ability, MnPC and MnPVA showed more potent immunocompetence and antitumor activity than Mn
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central |
| subjects | Adenosine diphosphate Anticancer properties Cancer Cancer therapies Chemistry Chlorine Cytoplasm Damage Deoxyribonucleic acid DNA DNA damage Fragments Immune system Lymphocytes Macrophages Manganese ions Ribose Stimulators |
| title | Manganese(ii) complexes stimulate antitumor immunity via aggravating DNA damage and activating the cGAS-STING pathway |
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