The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells
Combination antitumor treatments are essential parts of modern tumor therapy as-compared to monotherapies-(i) they are more effective; (ii) the dose of the compounds can be reduced; and (iii) therefore the side effects are improved. Our research group previously demonstrated the antitumor character...
Gespeichert in:
| Veröffentlicht in: | Pharmaceuticals (Basel, Switzerland) Switzerland), 2021-08, Vol.14 (8), p.820, Article 820 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 8 |
| container_start_page | 820 |
| container_title | Pharmaceuticals (Basel, Switzerland) |
| container_volume | 14 |
| creator | Takacs, Angela Szasz, Zsofia Kalabay, Marton Barany, Peter Csampai, Antal Hegyesi, Hargita Lang, Orsolya Lajko, Eszter Kohidai, Laszlo |
| description | Combination antitumor treatments are essential parts of modern tumor therapy as-compared to monotherapies-(i) they are more effective; (ii) the dose of the compounds can be reduced; and (iii) therefore the side effects are improved. Our research group previously demonstrated the antitumor character of bortezomib (BOZ) in A2058 melanoma cells. Unfortunately, dose-related side effects are common during BOZ therapy, which could be prevented by reducing the dose of BOZ. This study aimed to characterize synergistic combinations of BOZ with a TRAIL (TNF-related apoptosis-inducing ligand)-inducing compound (TIC10), where the doses can be cut down but the efficacy is preserved. Endpoint cell viability assays were performed on A2058 cells, and synergism of BOZ and TIC10 was observed after 72 h. Synergism was further validated in a real-time impedimetric assay, and our results showed that BOZ-treated melanoma cells survived the treatment, an effect not registered in the co-treatments. Treatment with the combinations resulted in increased apoptosis, which was not accompanied by enhanced LDH release. Nevertheless, the expression of death receptor 5 (DR5) was increased on the cell surface without transcriptional regulation. In summary, our findings support the theory that the application of BOZ and TIC10 in combination could provide higher efficacy in vitro. |
| doi_str_mv | 10.3390/ph14080820 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8399995</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_aaf840b408d6461f9008a8261e8e190d</doaj_id><sourcerecordid>2565488142</sourcerecordid><originalsourceid>FETCH-LOGICAL-c449t-ac96f5c2a1cbf7c86f19a162a0628e4d904581ed1e9f54ba720f06b03b458143</originalsourceid><addsrcrecordid>eNqNkUFvEzEQhVcIREvhwi9YiQuiCoy9Xse-IIVVgUitOJC7Neu1E0e7drCdVuHX45CqUE744tH4e0-eN1X1msD7ppHwYbchDAQICk-qc8IomwnK5k__qs-qFyltAdo5YeR5ddYw1hJJ5ufVzWpj6u8Hb-Lapex0vdDZ3bp8qIOtP4WYzc8wub5GP9SrZUegxjU6n3K9oNCK-saM6MOEdWfGMb2snlkck3l1f19Uq89Xq-7r7Prbl2W3uJ5pxmSeoZbctpoi0b2da8EtkUg4ReBUGDZIYK0gZiBG2pb1OKdggffQ9Mc-ay6q5cl2CLhVu-gmjAcV0KnfjRDXCmMZZjQK0QoGfcln4IwTKwEECsqJEYZIGIrXx5PXbt9PZtDG54jjI9PHL95t1DrcKtHIctpi8PbeIIYfe5OymlzSJQ30JuyToi3nwBglsqBv_kG3YR99SepItUyU4Wih3p0oHUNK0diHzxBQx4WrPwsvsDjBd6YPNmlnvDYPAgDgQgreNKUC0rmM2QXfhb3PRXr5_9LmF7M_uek</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2565488142</pqid></control><display><type>article</type><title>The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells</title><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>PubMed Central</source><creator>Takacs, Angela ; Szasz, Zsofia ; Kalabay, Marton ; Barany, Peter ; Csampai, Antal ; Hegyesi, Hargita ; Lang, Orsolya ; Lajko, Eszter ; Kohidai, Laszlo</creator><creatorcontrib>Takacs, Angela ; Szasz, Zsofia ; Kalabay, Marton ; Barany, Peter ; Csampai, Antal ; Hegyesi, Hargita ; Lang, Orsolya ; Lajko, Eszter ; Kohidai, Laszlo</creatorcontrib><description>Combination antitumor treatments are essential parts of modern tumor therapy as-compared to monotherapies-(i) they are more effective; (ii) the dose of the compounds can be reduced; and (iii) therefore the side effects are improved. Our research group previously demonstrated the antitumor character of bortezomib (BOZ) in A2058 melanoma cells. Unfortunately, dose-related side effects are common during BOZ therapy, which could be prevented by reducing the dose of BOZ. This study aimed to characterize synergistic combinations of BOZ with a TRAIL (TNF-related apoptosis-inducing ligand)-inducing compound (TIC10), where the doses can be cut down but the efficacy is preserved. Endpoint cell viability assays were performed on A2058 cells, and synergism of BOZ and TIC10 was observed after 72 h. Synergism was further validated in a real-time impedimetric assay, and our results showed that BOZ-treated melanoma cells survived the treatment, an effect not registered in the co-treatments. Treatment with the combinations resulted in increased apoptosis, which was not accompanied by enhanced LDH release. Nevertheless, the expression of death receptor 5 (DR5) was increased on the cell surface without transcriptional regulation. In summary, our findings support the theory that the application of BOZ and TIC10 in combination could provide higher efficacy in vitro.</description><identifier>ISSN: 1424-8247</identifier><identifier>EISSN: 1424-8247</identifier><identifier>DOI: 10.3390/ph14080820</identifier><identifier>PMID: 34451917</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>antitumor efficacy ; Apoptosis ; bortezomib ; Cancer ; Chemistry, Medicinal ; combination therapy ; Cytotoxicity ; Drug dosages ; Experiments ; Kinases ; Life Sciences & Biomedicine ; Ligands ; Melanoma ; Multiple myeloma ; Pharmacology & Pharmacy ; Proteins ; Science & Technology ; TIC10</subject><ispartof>Pharmaceuticals (Basel, Switzerland), 2021-08, Vol.14 (8), p.820, Article 820</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>3</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000689863300001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c449t-ac96f5c2a1cbf7c86f19a162a0628e4d904581ed1e9f54ba720f06b03b458143</citedby><cites>FETCH-LOGICAL-c449t-ac96f5c2a1cbf7c86f19a162a0628e4d904581ed1e9f54ba720f06b03b458143</cites><orcidid>0000-0003-2107-7309 ; 0000-0002-4796-4646 ; 0000-0002-9002-0296</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/PMC8399995/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399995/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,27928,27929,53795,53797</link.rule.ids></links><search><creatorcontrib>Takacs, Angela</creatorcontrib><creatorcontrib>Szasz, Zsofia</creatorcontrib><creatorcontrib>Kalabay, Marton</creatorcontrib><creatorcontrib>Barany, Peter</creatorcontrib><creatorcontrib>Csampai, Antal</creatorcontrib><creatorcontrib>Hegyesi, Hargita</creatorcontrib><creatorcontrib>Lang, Orsolya</creatorcontrib><creatorcontrib>Lajko, Eszter</creatorcontrib><creatorcontrib>Kohidai, Laszlo</creatorcontrib><title>The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells</title><title>Pharmaceuticals (Basel, Switzerland)</title><addtitle>PHARMACEUTICALS-BASE</addtitle><description>Combination antitumor treatments are essential parts of modern tumor therapy as-compared to monotherapies-(i) they are more effective; (ii) the dose of the compounds can be reduced; and (iii) therefore the side effects are improved. Our research group previously demonstrated the antitumor character of bortezomib (BOZ) in A2058 melanoma cells. Unfortunately, dose-related side effects are common during BOZ therapy, which could be prevented by reducing the dose of BOZ. This study aimed to characterize synergistic combinations of BOZ with a TRAIL (TNF-related apoptosis-inducing ligand)-inducing compound (TIC10), where the doses can be cut down but the efficacy is preserved. Endpoint cell viability assays were performed on A2058 cells, and synergism of BOZ and TIC10 was observed after 72 h. Synergism was further validated in a real-time impedimetric assay, and our results showed that BOZ-treated melanoma cells survived the treatment, an effect not registered in the co-treatments. Treatment with the combinations resulted in increased apoptosis, which was not accompanied by enhanced LDH release. Nevertheless, the expression of death receptor 5 (DR5) was increased on the cell surface without transcriptional regulation. In summary, our findings support the theory that the application of BOZ and TIC10 in combination could provide higher efficacy in vitro.</description><subject>antitumor efficacy</subject><subject>Apoptosis</subject><subject>bortezomib</subject><subject>Cancer</subject><subject>Chemistry, Medicinal</subject><subject>combination therapy</subject><subject>Cytotoxicity</subject><subject>Drug dosages</subject><subject>Experiments</subject><subject>Kinases</subject><subject>Life Sciences & Biomedicine</subject><subject>Ligands</subject><subject>Melanoma</subject><subject>Multiple myeloma</subject><subject>Pharmacology & Pharmacy</subject><subject>Proteins</subject><subject>Science & Technology</subject><subject>TIC10</subject><issn>1424-8247</issn><issn>1424-8247</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>DOA</sourceid><recordid>eNqNkUFvEzEQhVcIREvhwi9YiQuiCoy9Xse-IIVVgUitOJC7Neu1E0e7drCdVuHX45CqUE744tH4e0-eN1X1msD7ppHwYbchDAQICk-qc8IomwnK5k__qs-qFyltAdo5YeR5ddYw1hJJ5ufVzWpj6u8Hb-Lapex0vdDZ3bp8qIOtP4WYzc8wub5GP9SrZUegxjU6n3K9oNCK-saM6MOEdWfGMb2snlkck3l1f19Uq89Xq-7r7Prbl2W3uJ5pxmSeoZbctpoi0b2da8EtkUg4ReBUGDZIYK0gZiBG2pb1OKdggffQ9Mc-ay6q5cl2CLhVu-gmjAcV0KnfjRDXCmMZZjQK0QoGfcln4IwTKwEECsqJEYZIGIrXx5PXbt9PZtDG54jjI9PHL95t1DrcKtHIctpi8PbeIIYfe5OymlzSJQ30JuyToi3nwBglsqBv_kG3YR99SepItUyU4Wih3p0oHUNK0diHzxBQx4WrPwsvsDjBd6YPNmlnvDYPAgDgQgreNKUC0rmM2QXfhb3PRXr5_9LmF7M_uek</recordid><startdate>20210820</startdate><enddate>20210820</enddate><creator>Takacs, Angela</creator><creator>Szasz, Zsofia</creator><creator>Kalabay, Marton</creator><creator>Barany, Peter</creator><creator>Csampai, Antal</creator><creator>Hegyesi, Hargita</creator><creator>Lang, Orsolya</creator><creator>Lajko, Eszter</creator><creator>Kohidai, Laszlo</creator><general>Mdpi</general><general>MDPI AG</general><general>MDPI</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7XB</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2107-7309</orcidid><orcidid>https://orcid.org/0000-0002-4796-4646</orcidid><orcidid>https://orcid.org/0000-0002-9002-0296</orcidid></search><sort><creationdate>20210820</creationdate><title>The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells</title><author>Takacs, Angela ; Szasz, Zsofia ; Kalabay, Marton ; Barany, Peter ; Csampai, Antal ; Hegyesi, Hargita ; Lang, Orsolya ; Lajko, Eszter ; Kohidai, Laszlo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-ac96f5c2a1cbf7c86f19a162a0628e4d904581ed1e9f54ba720f06b03b458143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>antitumor efficacy</topic><topic>Apoptosis</topic><topic>bortezomib</topic><topic>Cancer</topic><topic>Chemistry, Medicinal</topic><topic>combination therapy</topic><topic>Cytotoxicity</topic><topic>Drug dosages</topic><topic>Experiments</topic><topic>Kinases</topic><topic>Life Sciences & Biomedicine</topic><topic>Ligands</topic><topic>Melanoma</topic><topic>Multiple myeloma</topic><topic>Pharmacology & Pharmacy</topic><topic>Proteins</topic><topic>Science & Technology</topic><topic>TIC10</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takacs, Angela</creatorcontrib><creatorcontrib>Szasz, Zsofia</creatorcontrib><creatorcontrib>Kalabay, Marton</creatorcontrib><creatorcontrib>Barany, Peter</creatorcontrib><creatorcontrib>Csampai, Antal</creatorcontrib><creatorcontrib>Hegyesi, Hargita</creatorcontrib><creatorcontrib>Lang, Orsolya</creatorcontrib><creatorcontrib>Lajko, Eszter</creatorcontrib><creatorcontrib>Kohidai, Laszlo</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Access via ProQuest (Open Access)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Pharmaceuticals (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takacs, Angela</au><au>Szasz, Zsofia</au><au>Kalabay, Marton</au><au>Barany, Peter</au><au>Csampai, Antal</au><au>Hegyesi, Hargita</au><au>Lang, Orsolya</au><au>Lajko, Eszter</au><au>Kohidai, Laszlo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells</atitle><jtitle>Pharmaceuticals (Basel, Switzerland)</jtitle><stitle>PHARMACEUTICALS-BASE</stitle><date>2021-08-20</date><risdate>2021</risdate><volume>14</volume><issue>8</issue><spage>820</spage><pages>820-</pages><artnum>820</artnum><issn>1424-8247</issn><eissn>1424-8247</eissn><abstract>Combination antitumor treatments are essential parts of modern tumor therapy as-compared to monotherapies-(i) they are more effective; (ii) the dose of the compounds can be reduced; and (iii) therefore the side effects are improved. Our research group previously demonstrated the antitumor character of bortezomib (BOZ) in A2058 melanoma cells. Unfortunately, dose-related side effects are common during BOZ therapy, which could be prevented by reducing the dose of BOZ. This study aimed to characterize synergistic combinations of BOZ with a TRAIL (TNF-related apoptosis-inducing ligand)-inducing compound (TIC10), where the doses can be cut down but the efficacy is preserved. Endpoint cell viability assays were performed on A2058 cells, and synergism of BOZ and TIC10 was observed after 72 h. Synergism was further validated in a real-time impedimetric assay, and our results showed that BOZ-treated melanoma cells survived the treatment, an effect not registered in the co-treatments. Treatment with the combinations resulted in increased apoptosis, which was not accompanied by enhanced LDH release. Nevertheless, the expression of death receptor 5 (DR5) was increased on the cell surface without transcriptional regulation. In summary, our findings support the theory that the application of BOZ and TIC10 in combination could provide higher efficacy in vitro.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>34451917</pmid><doi>10.3390/ph14080820</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-2107-7309</orcidid><orcidid>https://orcid.org/0000-0002-4796-4646</orcidid><orcidid>https://orcid.org/0000-0002-9002-0296</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1424-8247 |
| ispartof | Pharmaceuticals (Basel, Switzerland), 2021-08, Vol.14 (8), p.820, Article 820 |
| issn | 1424-8247 1424-8247 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8399995 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | antitumor efficacy Apoptosis bortezomib Cancer Chemistry, Medicinal combination therapy Cytotoxicity Drug dosages Experiments Kinases Life Sciences & Biomedicine Ligands Melanoma Multiple myeloma Pharmacology & Pharmacy Proteins Science & Technology TIC10 |
| title | The Synergistic Activity of Bortezomib and TIC10 against A2058 Melanoma Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T00%3A27%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Synergistic%20Activity%20of%20Bortezomib%20and%20TIC10%20against%20A2058%20Melanoma%20Cells&rft.jtitle=Pharmaceuticals%20(Basel,%20Switzerland)&rft.au=Takacs,%20Angela&rft.date=2021-08-20&rft.volume=14&rft.issue=8&rft.spage=820&rft.pages=820-&rft.artnum=820&rft.issn=1424-8247&rft.eissn=1424-8247&rft_id=info:doi/10.3390/ph14080820&rft_dat=%3Cproquest_pubme%3E2565488142%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2565488142&rft_id=info:pmid/34451917&rft_doaj_id=oai_doaj_org_article_aaf840b408d6461f9008a8261e8e190d&rfr_iscdi=true |