Deciphering the Interplay: Thieno[2,3- b ]pyridine's Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines
Ovarian cancer is among the most prevalent causes of mortality among women. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino- -(3-chloro-2-me...
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creator | Odak, Zdravko Marijan, Sandra Radan, Mila Pilkington, Lisa I Čikeš Botić, Monika Barker, David Reynisson, Jóhannes Leung, Euphemia Čikeš Čulić, Vedrana |
description | Ovarian cancer is among the most prevalent causes of mortality among women. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-
-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-
]quinoline-2-carboxamide (Compound
), was examined. The impacts of cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, on cancer stem cells (CSCs), marked as CD49f
, and non-CSCs (CD49f
) were explored. Treatment with Compound
reduced the percentage of CSCs compared to non-treated cells (
< 0.001). The functional impact of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. The glycophenotype changed in both cell lines, with increases or decreases in its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment with Compound
resulted in statistically meaningful increased apoptosis, including both early and late apoptosis (
< 0.001), suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The analysis revealed that the metabolic activity of treated cancer cells was lower compared to those of the control group (
< 0.001). |
doi_str_mv | 10.3390/ijms25136954 |
format | Article |
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-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-
]quinoline-2-carboxamide (Compound
), was examined. The impacts of cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, on cancer stem cells (CSCs), marked as CD49f
, and non-CSCs (CD49f
) were explored. Treatment with Compound
reduced the percentage of CSCs compared to non-treated cells (
< 0.001). The functional impact of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. The glycophenotype changed in both cell lines, with increases or decreases in its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment with Compound
resulted in statistically meaningful increased apoptosis, including both early and late apoptosis (
< 0.001), suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The analysis revealed that the metabolic activity of treated cancer cells was lower compared to those of the control group (
< 0.001).</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms25136954</identifier><identifier>PMID: 39000063</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Cell death ; Cell Line, Tumor ; Cytotoxicity ; Female ; Glycosphingolipids - metabolism ; Gynecology ; Humans ; Kinases ; Metabolome - drug effects ; Metabolomics - methods ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Ovarian cancer ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - metabolism ; Ovarian Neoplasms - pathology ; Pyridines - pharmacology ; Statistical significance ; Stem cells ; Tumors</subject><ispartof>International journal of molecular sciences, 2024-07, Vol.25 (13), p.6954</ispartof><rights>2024 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c211t-e712765d6566ecfe40d2b051eb258b9beb1d14bef8dc6a8941a335d819f37d6d3</cites><orcidid>0000-0002-6932-3188 ; 0000-0001-5821-6785 ; 0000-0001-8341-9760 ; 0000-0002-9292-3261 ; 0000-0003-2259-2871 ; 0000-0003-4174-9512 ; 0000-0002-4415-4410 ; 0000-0002-3425-6552 ; 0000-0001-7932-5817</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39000063$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Odak, Zdravko</creatorcontrib><creatorcontrib>Marijan, Sandra</creatorcontrib><creatorcontrib>Radan, Mila</creatorcontrib><creatorcontrib>Pilkington, Lisa I</creatorcontrib><creatorcontrib>Čikeš Botić, Monika</creatorcontrib><creatorcontrib>Barker, David</creatorcontrib><creatorcontrib>Reynisson, Jóhannes</creatorcontrib><creatorcontrib>Leung, Euphemia</creatorcontrib><creatorcontrib>Čikeš Čulić, Vedrana</creatorcontrib><title>Deciphering the Interplay: Thieno[2,3- b ]pyridine's Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Ovarian cancer is among the most prevalent causes of mortality among women. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-
-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-
]quinoline-2-carboxamide (Compound
), was examined. The impacts of cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, on cancer stem cells (CSCs), marked as CD49f
, and non-CSCs (CD49f
) were explored. Treatment with Compound
reduced the percentage of CSCs compared to non-treated cells (
< 0.001). The functional impact of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. The glycophenotype changed in both cell lines, with increases or decreases in its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment with Compound
resulted in statistically meaningful increased apoptosis, including both early and late apoptosis (
< 0.001), suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The analysis revealed that the metabolic activity of treated cancer cells was lower compared to those of the control group (
< 0.001).</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Cytotoxicity</subject><subject>Female</subject><subject>Glycosphingolipids - metabolism</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Kinases</subject><subject>Metabolome - drug effects</subject><subject>Metabolomics - methods</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Ovarian cancer</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Pyridines - pharmacology</subject><subject>Statistical significance</subject><subject>Stem cells</subject><subject>Tumors</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpNkTtv1EAUhS1ERB7QUaMrUaSxwzzs8ZouWkJYaVGapULImsc1Oyt7ZpiZRfHfyS_FKAHlNucW3zmnOEXxlpIrzjvywR6mxBrKRdfUL4ozWjNWESLal8_-0-I8pQMhjLOme1WcLr7lBD8rHj6htmGP0bqfkPcIG5cxhlHOH2G3t-j8d1byChT8CHO0xjq8TLCZgtQZvIPbcdY-hf1i96MN1sDNfYiYkvWuhPWcffb3Vts8l3AdfMg-2VSCdAa-YpbKj36yOoF1cPdbRisd7I6Tj7DGcYTtUpdeFyeDHBO-edKL4tvnm936S7W9u92sr7eVZpTmClvKWtEY0QiBesCaGKZIQ1GxZqU6hYoaWiscVkYLuepqKjlvzIp2A2-NMPyieP-YG6L_dcSU-4M_RrdU9py0HSc1YWKhykdKR59SxKEP0U4yzj0l_d9B-ueDLPi7p9CjmtD8h_8twP8Am_uIzQ</recordid><startdate>20240701</startdate><enddate>20240701</enddate><creator>Odak, Zdravko</creator><creator>Marijan, Sandra</creator><creator>Radan, Mila</creator><creator>Pilkington, Lisa I</creator><creator>Čikeš Botić, Monika</creator><creator>Barker, David</creator><creator>Reynisson, Jóhannes</creator><creator>Leung, Euphemia</creator><creator>Čikeš Čulić, Vedrana</creator><general>MDPI AG</general><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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><orcidid>https://orcid.org/0000-0002-6932-3188</orcidid><orcidid>https://orcid.org/0000-0001-5821-6785</orcidid><orcidid>https://orcid.org/0000-0001-8341-9760</orcidid><orcidid>https://orcid.org/0000-0002-9292-3261</orcidid><orcidid>https://orcid.org/0000-0003-2259-2871</orcidid><orcidid>https://orcid.org/0000-0003-4174-9512</orcidid><orcidid>https://orcid.org/0000-0002-4415-4410</orcidid><orcidid>https://orcid.org/0000-0002-3425-6552</orcidid><orcidid>https://orcid.org/0000-0001-7932-5817</orcidid></search><sort><creationdate>20240701</creationdate><title>Deciphering the Interplay: Thieno[2,3- b ]pyridine's Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines</title><author>Odak, Zdravko ; Marijan, Sandra ; Radan, Mila ; Pilkington, Lisa I ; Čikeš Botić, Monika ; Barker, David ; Reynisson, Jóhannes ; Leung, Euphemia ; Čikeš Čulić, Vedrana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c211t-e712765d6566ecfe40d2b051eb258b9beb1d14bef8dc6a8941a335d819f37d6d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Cytotoxicity</topic><topic>Female</topic><topic>Glycosphingolipids - metabolism</topic><topic>Gynecology</topic><topic>Humans</topic><topic>Kinases</topic><topic>Metabolome - drug effects</topic><topic>Metabolomics - methods</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Ovarian cancer</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - metabolism</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Pyridines - pharmacology</topic><topic>Statistical significance</topic><topic>Stem cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Odak, Zdravko</creatorcontrib><creatorcontrib>Marijan, Sandra</creatorcontrib><creatorcontrib>Radan, Mila</creatorcontrib><creatorcontrib>Pilkington, Lisa I</creatorcontrib><creatorcontrib>Čikeš Botić, Monika</creatorcontrib><creatorcontrib>Barker, David</creatorcontrib><creatorcontrib>Reynisson, Jóhannes</creatorcontrib><creatorcontrib>Leung, Euphemia</creatorcontrib><creatorcontrib>Čikeš Čulić, Vedrana</creatorcontrib><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</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>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content 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 Basic</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Odak, Zdravko</au><au>Marijan, Sandra</au><au>Radan, Mila</au><au>Pilkington, Lisa I</au><au>Čikeš Botić, Monika</au><au>Barker, David</au><au>Reynisson, Jóhannes</au><au>Leung, Euphemia</au><au>Čikeš Čulić, Vedrana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deciphering the Interplay: Thieno[2,3- b ]pyridine's Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2024-07-01</date><risdate>2024</risdate><volume>25</volume><issue>13</issue><spage>6954</spage><pages>6954-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Ovarian cancer is among the most prevalent causes of mortality among women. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-
-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-
]quinoline-2-carboxamide (Compound
), was examined. The impacts of cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, on cancer stem cells (CSCs), marked as CD49f
, and non-CSCs (CD49f
) were explored. Treatment with Compound
reduced the percentage of CSCs compared to non-treated cells (
< 0.001). The functional impact of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. The glycophenotype changed in both cell lines, with increases or decreases in its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment with Compound
resulted in statistically meaningful increased apoptosis, including both early and late apoptosis (
< 0.001), suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The analysis revealed that the metabolic activity of treated cancer cells was lower compared to those of the control group (
< 0.001).</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39000063</pmid><doi>10.3390/ijms25136954</doi><orcidid>https://orcid.org/0000-0002-6932-3188</orcidid><orcidid>https://orcid.org/0000-0001-5821-6785</orcidid><orcidid>https://orcid.org/0000-0001-8341-9760</orcidid><orcidid>https://orcid.org/0000-0002-9292-3261</orcidid><orcidid>https://orcid.org/0000-0003-2259-2871</orcidid><orcidid>https://orcid.org/0000-0003-4174-9512</orcidid><orcidid>https://orcid.org/0000-0002-4415-4410</orcidid><orcidid>https://orcid.org/0000-0002-3425-6552</orcidid><orcidid>https://orcid.org/0000-0001-7932-5817</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Cell death Cell Line, Tumor Cytotoxicity Female Glycosphingolipids - metabolism Gynecology Humans Kinases Metabolome - drug effects Metabolomics - methods Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Ovarian cancer Ovarian Neoplasms - drug therapy Ovarian Neoplasms - metabolism Ovarian Neoplasms - pathology Pyridines - pharmacology Statistical significance Stem cells Tumors |
title | Deciphering the Interplay: Thieno[2,3- b ]pyridine's Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines |
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