Somatostatin receptor mediated targeting of acute myeloid leukemia by photodynamic metal complexes for light induced apoptosis
Acute myeloid leukemia (AML) is characterized by relapse and treatment resistance in a major fraction of patients, underlining the need of innovative AML targeting therapies. Here we analysed the therapeutic potential of an innovative biohybrid consisting of the tumor-associated peptide somatostatin...
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| Veröffentlicht in: | Scientific reports 2020-01, Vol.10 (1), p.371-371, Article 371 |
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| creator | Vegi, Naidu M. Chakrabortty, Sabyasachi Zegota, Maksymilian M. Kuan, Seah Ling Stumper, Anne Rawat, Vijay P. S. Sieste, Stefanie Buske, Christian Rau, Sven Weil, Tanja Feuring-Buske, Michaela |
| description | Acute myeloid leukemia (AML) is characterized by relapse and treatment resistance in a major fraction of patients, underlining the need of innovative AML targeting therapies. Here we analysed the therapeutic potential of an innovative biohybrid consisting of the tumor-associated peptide somatostatin and the photosensitizer ruthenium in AML cell lines and primary AML patient samples. Selective toxicity was analyzed by using CD34 enriched cord blood cells as control. Treatment of OCI AML3, HL60 and THP1 resulted in a 92, and 99 and 97% decrease in clonogenic growth compared to the controls. Primary AML cells demonstrated a major response with a 74 to 99% reduction in clonogenicity in 5 of 6 patient samples. In contrast, treatment of CD34
+
CB cells resulted in substantially less reduction in colony numbers. Subcellular localization assays of RU-SST in OCI-AML3 cells confirmed strong co-localization of RU-SST in the lysosomes compared to the other cellular organelles. Our data demonstrate that conjugation of a Ruthenium complex with somatostatin is efficiently eradicating LSC candidates of patients with AML. This indicates that receptor mediated lysosomal accumulation of photodynamic metal complexes is a highly attractive approach for targeting AML cells. |
| doi_str_mv | 10.1038/s41598-019-57172-6 |
| format | Article |
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+
CB cells resulted in substantially less reduction in colony numbers. Subcellular localization assays of RU-SST in OCI-AML3 cells confirmed strong co-localization of RU-SST in the lysosomes compared to the other cellular organelles. Our data demonstrate that conjugation of a Ruthenium complex with somatostatin is efficiently eradicating LSC candidates of patients with AML. This indicates that receptor mediated lysosomal accumulation of photodynamic metal complexes is a highly attractive approach for targeting AML cells.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-57172-6</identifier><identifier>PMID: 31941913</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/100 ; 13/106 ; 13/31 ; 14/19 ; 38/39 ; 631/154/152 ; 631/67/1990/283 ; Acute myeloid leukemia ; Adult ; Aged ; Apoptosis ; Blood cells ; CD34 antigen ; Cell Line, Tumor ; Cord blood ; Drug Stability ; Female ; Fetal Blood - metabolism ; Humanities and Social Sciences ; Humans ; Leukemia ; Leukemia, Myeloid, Acute - therapy ; Localization ; Lysosomes ; Lysosomes - metabolism ; Male ; Metal complexes ; Middle Aged ; multidisciplinary ; Myeloid leukemia ; Organelles ; Photochemotherapy ; Photosensitizing Agents - chemistry ; Photosensitizing Agents - therapeutic use ; Reactive Oxygen Species - metabolism ; Receptors, Somatostatin - metabolism ; Ruthenium ; Ruthenium - therapeutic use ; Science ; Science (multidisciplinary) ; Somatostatin ; Somatostatin - therapeutic use ; Toxicity ; Treatment resistance</subject><ispartof>Scientific reports, 2020-01, Vol.10 (1), p.371-371, Article 371</ispartof><rights>The Author(s) 2020</rights><rights>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-c474t-fbe2e35ddab1b68a9b503471cfbbc49dc47ede0ca1aa78a00974444a7891a9d93</citedby><cites>FETCH-LOGICAL-c474t-fbe2e35ddab1b68a9b503471cfbbc49dc47ede0ca1aa78a00974444a7891a9d93</cites><orcidid>0000-0002-2759-2208 ; 0000-0003-3945-4491 ; 0000-0001-9635-6009</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/PMC6962389/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962389/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31941913$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vegi, Naidu M.</creatorcontrib><creatorcontrib>Chakrabortty, Sabyasachi</creatorcontrib><creatorcontrib>Zegota, Maksymilian M.</creatorcontrib><creatorcontrib>Kuan, Seah Ling</creatorcontrib><creatorcontrib>Stumper, Anne</creatorcontrib><creatorcontrib>Rawat, Vijay P. S.</creatorcontrib><creatorcontrib>Sieste, Stefanie</creatorcontrib><creatorcontrib>Buske, Christian</creatorcontrib><creatorcontrib>Rau, Sven</creatorcontrib><creatorcontrib>Weil, Tanja</creatorcontrib><creatorcontrib>Feuring-Buske, Michaela</creatorcontrib><title>Somatostatin receptor mediated targeting of acute myeloid leukemia by photodynamic metal complexes for light induced apoptosis</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Acute myeloid leukemia (AML) is characterized by relapse and treatment resistance in a major fraction of patients, underlining the need of innovative AML targeting therapies. Here we analysed the therapeutic potential of an innovative biohybrid consisting of the tumor-associated peptide somatostatin and the photosensitizer ruthenium in AML cell lines and primary AML patient samples. Selective toxicity was analyzed by using CD34 enriched cord blood cells as control. Treatment of OCI AML3, HL60 and THP1 resulted in a 92, and 99 and 97% decrease in clonogenic growth compared to the controls. Primary AML cells demonstrated a major response with a 74 to 99% reduction in clonogenicity in 5 of 6 patient samples. In contrast, treatment of CD34
+
CB cells resulted in substantially less reduction in colony numbers. Subcellular localization assays of RU-SST in OCI-AML3 cells confirmed strong co-localization of RU-SST in the lysosomes compared to the other cellular organelles. Our data demonstrate that conjugation of a Ruthenium complex with somatostatin is efficiently eradicating LSC candidates of patients with AML. This indicates that receptor mediated lysosomal accumulation of photodynamic metal complexes is a highly attractive approach for targeting AML cells.</description><subject>13/100</subject><subject>13/106</subject><subject>13/31</subject><subject>14/19</subject><subject>38/39</subject><subject>631/154/152</subject><subject>631/67/1990/283</subject><subject>Acute myeloid leukemia</subject><subject>Adult</subject><subject>Aged</subject><subject>Apoptosis</subject><subject>Blood cells</subject><subject>CD34 antigen</subject><subject>Cell Line, Tumor</subject><subject>Cord blood</subject><subject>Drug Stability</subject><subject>Female</subject><subject>Fetal Blood - metabolism</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - therapy</subject><subject>Localization</subject><subject>Lysosomes</subject><subject>Lysosomes - metabolism</subject><subject>Male</subject><subject>Metal complexes</subject><subject>Middle Aged</subject><subject>multidisciplinary</subject><subject>Myeloid leukemia</subject><subject>Organelles</subject><subject>Photochemotherapy</subject><subject>Photosensitizing Agents - chemistry</subject><subject>Photosensitizing Agents - therapeutic use</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Receptors, Somatostatin - metabolism</subject><subject>Ruthenium</subject><subject>Ruthenium - therapeutic use</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Somatostatin</subject><subject>Somatostatin - therapeutic use</subject><subject>Toxicity</subject><subject>Treatment resistance</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kUtv1TAQhSMEolXpH2CBLLFhE_ArD2-QUAUFqRILYG1N7EmuixMH20HcDb8d395SCgtm45HOmW88OlX1lNGXjIr-VZKsUX1NmaqbjnW8bh9Up5zKpuaC84f3-pPqPKVrWqrhSjL1uDoR7NAwcVr9_BRmyCFlyG4hEQ2uOUQyo3WQ0ZIMccIiTSSMBMyWkcx79MFZ4nH7irMDMuzJugs52P0CszNlOIMnJsyrxx-YyFiA3k27TNxiN1OosIayJrn0pHo0gk94fvueVV_evf188b6--nj54eLNVW1kJ3M9DshRNNbCwIa2BzU0VMiOmXEYjFS2uNAiNcAAuh4oVZ0sVXrFQFklzqrXR-66DeU2g0uO4PUa3QxxrwM4_beyuJ2ewnfdqpaL_gB4cQuI4duGKevZJYPew4JhS5oLoTrFesaK9fk_1uuwxaWcV1xS8J724gDkR5eJIaWI491nGNWHhPUxYV0S1jcJ67YMPbt_xt3I7zyLQRwNqUjLhPHP7v9gfwEzPLXM</recordid><startdate>20200115</startdate><enddate>20200115</enddate><creator>Vegi, Naidu M.</creator><creator>Chakrabortty, Sabyasachi</creator><creator>Zegota, Maksymilian M.</creator><creator>Kuan, Seah Ling</creator><creator>Stumper, Anne</creator><creator>Rawat, Vijay P. 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S.</au><au>Sieste, Stefanie</au><au>Buske, Christian</au><au>Rau, Sven</au><au>Weil, Tanja</au><au>Feuring-Buske, Michaela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Somatostatin receptor mediated targeting of acute myeloid leukemia by photodynamic metal complexes for light induced apoptosis</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-01-15</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>371</spage><epage>371</epage><pages>371-371</pages><artnum>371</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Acute myeloid leukemia (AML) is characterized by relapse and treatment resistance in a major fraction of patients, underlining the need of innovative AML targeting therapies. Here we analysed the therapeutic potential of an innovative biohybrid consisting of the tumor-associated peptide somatostatin and the photosensitizer ruthenium in AML cell lines and primary AML patient samples. Selective toxicity was analyzed by using CD34 enriched cord blood cells as control. Treatment of OCI AML3, HL60 and THP1 resulted in a 92, and 99 and 97% decrease in clonogenic growth compared to the controls. Primary AML cells demonstrated a major response with a 74 to 99% reduction in clonogenicity in 5 of 6 patient samples. In contrast, treatment of CD34
+
CB cells resulted in substantially less reduction in colony numbers. Subcellular localization assays of RU-SST in OCI-AML3 cells confirmed strong co-localization of RU-SST in the lysosomes compared to the other cellular organelles. Our data demonstrate that conjugation of a Ruthenium complex with somatostatin is efficiently eradicating LSC candidates of patients with AML. This indicates that receptor mediated lysosomal accumulation of photodynamic metal complexes is a highly attractive approach for targeting AML cells.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31941913</pmid><doi>10.1038/s41598-019-57172-6</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-2759-2208</orcidid><orcidid>https://orcid.org/0000-0003-3945-4491</orcidid><orcidid>https://orcid.org/0000-0001-9635-6009</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 13/100 13/106 13/31 14/19 38/39 631/154/152 631/67/1990/283 Acute myeloid leukemia Adult Aged Apoptosis Blood cells CD34 antigen Cell Line, Tumor Cord blood Drug Stability Female Fetal Blood - metabolism Humanities and Social Sciences Humans Leukemia Leukemia, Myeloid, Acute - therapy Localization Lysosomes Lysosomes - metabolism Male Metal complexes Middle Aged multidisciplinary Myeloid leukemia Organelles Photochemotherapy Photosensitizing Agents - chemistry Photosensitizing Agents - therapeutic use Reactive Oxygen Species - metabolism Receptors, Somatostatin - metabolism Ruthenium Ruthenium - therapeutic use Science Science (multidisciplinary) Somatostatin Somatostatin - therapeutic use Toxicity Treatment resistance |
| title | Somatostatin receptor mediated targeting of acute myeloid leukemia by photodynamic metal complexes for light induced apoptosis |
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