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Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction | Anticancer Research
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Delinasios), All rights reserved." /> <meta name="DC.AccessRights" content="restricted" /> <meta name="DC.Description" content="Background/Aim: Ovarian cancer remains a significant challenge due to its high mortality rate and poor prognosis, especially in advanced stages. Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer. Materials and Methods: The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes. Results: Fostamatinib treatment resulted in a dose- and time-dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNEL-positive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction. Conclusion: Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes." /> <meta name="DC.Contributor" content="HYE MIN LEE" /> <meta name="DC.Contributor" content="HEE JIN CHO" /> <meta name="DC.Contributor" content="YUL MIN LEE" /> <meta name="DC.Contributor" content="HYUN JUNG KIM" /> <meta name="DC.Contributor" content="KYUN HEO" /> <meta name="article:published_time" content="2024-11-01" /> <meta name="article:section" content="Experimental Studies" /> <meta name="citation_title" content="Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction" /> <meta name="citation_abstract" lang="en" content="<p>Background/Aim: Ovarian cancer remains a significant challenge due to its high mortality rate and poor prognosis, especially in advanced stages. Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer. Materials and Methods: The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes. Results: Fostamatinib treatment resulted in a dose- and time-dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNEL-positive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction. Conclusion: Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes.</p>" /> <meta name="citation_journal_title" content="Anticancer Research" /> <meta name="citation_publisher" content="International Institute of Anticancer Research" /> <meta name="citation_publication_date" content="2024/11/01" /> <meta name="citation_mjid" content="anticanres;44/11/4895" /> <meta name="citation_id" content="44/11/4895" /> <meta name="citation_public_url" content="https://ar.iiarjournals.org/content/44/11/4895" /> <meta name="citation_abstract_html_url" content="https://ar.iiarjournals.org/content/44/11/4895.abstract" /> <meta name="citation_full_html_url" content="https://ar.iiarjournals.org/content/44/11/4895.full" /> <meta name="citation_pdf_url" content="https://ar.iiarjournals.org/content/anticanres/44/11/4895.full.pdf" /> <meta name="citation_issn" content="0250-7005" /> <meta name="citation_issn" content="1791-7530" /> <meta name="citation_doi" content="10.21873/anticanres.17315" /> <meta name="citation_pmid" content="39477304" /> <meta name="citation_volume" content="44" /> <meta name="citation_issue" content="11" /> <meta name="citation_article_type" content="Research Article" /> <meta name="citation_section" content="Experimental Studies" /> <meta name="citation_firstpage" content="4895" /> <meta name="citation_lastpage" content="4903" /> <meta name="citation_author" content="HYE MIN LEE" /> <meta name="citation_author_institution" content="Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;" /> <meta name="citation_author" content="HEE JIN CHO" /> <meta name="citation_author_institution" content="Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;" /> <meta name="citation_author" content="YUL MIN LEE" /> <meta name="citation_author_institution" content="Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;" /> <meta name="citation_author" content="HYUN JUNG KIM" /> <meta name="citation_author_institution" content="Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;" /> <meta name="citation_author_institution" content="Department of Biopharmaceutical Chemistry, Kookmin University, Seoul, Republic of Korea;" /> <meta name="citation_author_institution" content="Antibody Research Institute, Kookmin University, Seoul, Republic of Korea" /> <meta name="citation_author_email" content="hjkim423@kookmin.ac.kr" /> <meta name="citation_author" content="KYUN HEO" /> <meta name="citation_author_institution" content="Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;" /> <meta name="citation_author_institution" content="Department of Biopharmaceutical Chemistry, Kookmin University, Seoul, Republic of Korea;" /> <meta name="citation_author_institution" content="Antibody Research Institute, Kookmin University, Seoul, Republic of Korea" /> <meta name="citation_author_email" content="kyunheo@kookmin.ac.kr" /> <meta name="citation_reference" content="citation_journal_title=Best Pract Res Clin Obstet Gynaecol;citation_author=PM. 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Schaefer-Cutillo;citation_author=S. De Vos;citation_author=R. Sinha;citation_author=JP. Leonard;citation_author=LD. Cripe;citation_author=SA. Gregory;citation_author=MP. Sterba;citation_author=AM. Lowe;citation_author=R. Levy;citation_author=MA. Shipp;citation_title=Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia;citation_volume=115;citation_year=2010;citation_issue=13;citation_pmid=19965662;citation_doi=10.1182/blood-2009-08-236471" /> <meta name="twitter:title" content="Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction" /> <meta name="twitter:card" content="summary_large_image" /> <meta name="twitter:image" content="https://ar.iiarjournals.org/sites/default/files/highwire/anticanres/44/11.cover-source.jpg" /> <meta name="twitter:description" content="Background/Aim: Ovarian cancer remains a significant challenge due to its high mortality rate and poor prognosis, especially in advanced stages. Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer. Materials and Methods: The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes. Results: Fostamatinib treatment resulted in a dose- and time-dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNEL-positive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction. Conclusion: Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes." /> <meta name="og-title" property="og:title" content="Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction" /> <meta name="og-url" property="og:url" content="https://ar.iiarjournals.org/content/44/11/4895" /> <meta name="og-site-name" property="og:site_name" content="Anticancer Research" /> <meta name="og-description" property="og:description" content="Background/Aim: Ovarian cancer remains a significant challenge due to its high mortality rate and poor prognosis, especially in advanced stages. Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer. Materials and Methods: The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes. Results: Fostamatinib treatment resulted in a dose- and time-dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNEL-positive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction. Conclusion: Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes." /> <meta name="og-type" property="og:type" content="article" /> <meta name="og-image" property="og:image" content="https://ar.iiarjournals.org/sites/default/files/highwire/anticanres/44/11.cover-source.jpg" /> <link rel="shortlink" href="/node/82000" /> <link rel="shortcut icon" href="https://ar.iiarjournals.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon" /> <meta name="viewport" content="width=device-width, initial-scale=1" /> <title>Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction | Anticancer Research</title> <link type="text/css" rel="stylesheet" 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highwire-citation-highwire-article-top-a"> <div class="highwire-cite-overline"><span class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Experimental Studies</span></span></div> <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="anticanres;44/11/4895" data-atom-uri="/anticanres/44/11/4895.atom" data-request-view="full"></span></div> <h1 class="highwire-cite-title" id="page-title">Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction</h1> <div class="highwire-cite-authors"><span class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">HYE MIN LEE</span>, <span class="highwire-citation-author" data-delta="1">HEE JIN CHO</span>, <span class="highwire-citation-author" data-delta="2">YUL MIN LEE</span>, <span class="highwire-citation-author" data-delta="3">HYUN JUNG KIM</span> and <span class="highwire-citation-author" data-delta="4">KYUN HEO</span></span></div> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-journal highwire-cite-metadata">Anticancer Research </span><span class="highwire-cite-metadata-date highwire-cite-metadata">November 2024, </span><span class="highwire-cite-metadata-volume highwire-cite-metadata">44 </span><span class="highwire-cite-metadata-issue highwire-cite-metadata">(11) </span><span class="highwire-cite-metadata-pages highwire-cite-metadata">4895-4903; </span><span class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.21873/anticanres.17315 </span></div> <div class="highwire-cite-extras"><span class="highwire-foxycart-add-to-cart-ahah highwire-foxycart-add-to-cart-ahah" data-text="Add to Cart (%short-price)" data-apath="/anticanres/44/11/4895.atom" data-type="link" data-font-icon="" data-parent-id="81985"></span></div> </div> <div id="hw-article-author-popups-top-node-82000--2125441137" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">HYE MIN LEE </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=HYE%2BMIN%2BLEE%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=LEE%20HM&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AHYE%2BMIN%2BLEE%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">HEE JIN CHO </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=HEE%2BJIN%2BCHO%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=CHO%20HJ&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AHEE%2BJIN%2BCHO%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">YUL MIN LEE </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=YUL%2BMIN%2BLEE%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=LEE%20YM&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AYUL%2BMIN%2BLEE%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">HYUN JUNG KIM </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;</div><div class='author-affiliation'><span class='nlm-sup'>2</span>Department of Biopharmaceutical Chemistry, Kookmin University, Seoul, Republic of Korea;</div><div class='author-affiliation'><span class='nlm-sup'>3</span>Antibody Research Institute, Kookmin University, Seoul, Republic of Korea</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=HYUN%2BJUNG%2BKIM%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=KIM%20HJ&link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AHYUN%2BJUNG%2BKIM%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-corresp-email-link last"><span>For correspondence: <a href="mailto:hjkim423@kookmin.ac.kr" class="" data-icon-position="" data-hide-link-title="0">hjkim423@kookmin.ac.kr</a></span></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">KYUN HEO </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>1</span>Biopharmaceutical Chemistry Major, School of Applied Chemistry, Kookmin University, Seoul, Republic of Korea;</div><div class='author-affiliation'><span class='nlm-sup'>2</span>Department of Biopharmaceutical Chemistry, Kookmin University, Seoul, Republic of Korea;</div><div class='author-affiliation'><span class='nlm-sup'>3</span>Antibody Research Institute, Kookmin University, Seoul, Republic of Korea</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=KYUN%2BHEO%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a 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Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer. Materials and Methods: The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes. Results: Fostamatinib treatment resulted in a dose- and time-dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNEL-positive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction. Conclusion: Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as a repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes.</p></div><span class="kwd-group-title">Key Words:</span><ul class="kwd-group"><li class="kwd"><a href="/keyword/fostamatinib" class="hw-term hw-article-keyword hw-article-keyword-fostamatinib" rel="nofollow">Fostamatinib</a></li><li class="kwd"><a href="/keyword/ovarian-cancer" class="hw-term hw-article-keyword hw-article-keyword-ovarian-cancer" rel="nofollow">ovarian cancer</a></li><li class="kwd"><a href="/keyword/drug-repositioning" class="hw-term hw-article-keyword hw-article-keyword-drug-repositioning" rel="nofollow">drug repositioning</a></li><li class="kwd"><a href="/keyword/proliferation" class="hw-term hw-article-keyword hw-article-keyword-proliferation" rel="nofollow">proliferation</a></li><li class="kwd"><a href="/keyword/apoptosis" class="hw-term hw-article-keyword hw-article-keyword-apoptosis" rel="nofollow">apoptosis</a></li></ul><ul class="history-list"><li xmlns:hwp="http://schema.highwire.org/Journal" class="received" hwp:start="2024-09-15"><span class="received-label">Received </span>September 15, 2024.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="rev-recd" hwp:start="2024-10-04"><span class="rev-recd-label">Revision received </span>October 4, 2024.</li><li xmlns:hwp="http://schema.highwire.org/Journal" class="accepted" hwp:start="2024-10-07"><span class="accepted-label">Accepted </span>October 7, 2024.</li></ul><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">Copyright 漏 2024 International Institute of Anticancer Research (Dr. George J. 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