Cysteamine Suppresses Cancer Cell Invasion and Migration in Glioblastoma through Inhibition of Matrix Metalloproteinase Activity
Glioblastoma (GBM) cells are highly invasive, infiltrating the surrounding normal brain tissue, thereby limiting the efficacy of surgical resection and focal radiotherapy. Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treat...
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| Veröffentlicht in: | Cancers 2024-05, Vol.16 (11), p.2029 |
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| creator | Jung, Jinkyu Celiku, Orieta Rubin, Benjamin I Gilbert, Mark R |
| description | Glioblastoma (GBM) cells are highly invasive, infiltrating the surrounding normal brain tissue, thereby limiting the efficacy of surgical resection and focal radiotherapy. Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine's inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment. |
| doi_str_mv | 10.3390/cancers16112029 |
| format | Article |
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Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine's inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers16112029</identifier><identifier>PMID: 38893149</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Angiogenesis ; Antineoplastic drugs ; Brain cancer ; Brain research ; Brain tumors ; Cancer therapies ; Cell death ; Cell growth ; Cell migration ; Chemical bonds ; Computational neuroscience ; Cysteamine ; Cystinosis ; Cytotoxicity ; Development and progression ; Drug therapy ; Enzymes ; Extracellular matrix ; Gelatinase A ; Gelatinase B ; Gene expression ; Glioblastoma ; Glioblastoma multiforme ; Glioma ; Health aspects ; Mammalian cells ; Matrix metalloproteinase ; Metalloproteinase ; Metastases ; Metastasis ; Molecular modelling ; Protease inhibitors ; Radiation therapy ; Testing ; Toxicity ; Tumors</subject><ispartof>Cancers, 2024-05, Vol.16 (11), p.2029</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><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><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c373t-4b1a1c81b7864850695f6a23d51d92aeb8f9f1f4a54b128b6354887914a9be033</cites><orcidid>0000-0002-0500-1032 ; 0000-0002-8359-6246</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/PMC11171184/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171184/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38893149$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jung, Jinkyu</creatorcontrib><creatorcontrib>Celiku, Orieta</creatorcontrib><creatorcontrib>Rubin, Benjamin I</creatorcontrib><creatorcontrib>Gilbert, Mark R</creatorcontrib><title>Cysteamine Suppresses Cancer Cell Invasion and Migration in Glioblastoma through Inhibition of Matrix Metalloproteinase Activity</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Glioblastoma (GBM) cells are highly invasive, infiltrating the surrounding normal brain tissue, thereby limiting the efficacy of surgical resection and focal radiotherapy. Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine's inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment.</description><subject>Angiogenesis</subject><subject>Antineoplastic drugs</subject><subject>Brain cancer</subject><subject>Brain research</subject><subject>Brain tumors</subject><subject>Cancer therapies</subject><subject>Cell death</subject><subject>Cell growth</subject><subject>Cell migration</subject><subject>Chemical bonds</subject><subject>Computational neuroscience</subject><subject>Cysteamine</subject><subject>Cystinosis</subject><subject>Cytotoxicity</subject><subject>Development and progression</subject><subject>Drug therapy</subject><subject>Enzymes</subject><subject>Extracellular matrix</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Gene expression</subject><subject>Glioblastoma</subject><subject>Glioblastoma multiforme</subject><subject>Glioma</subject><subject>Health aspects</subject><subject>Mammalian cells</subject><subject>Matrix metalloproteinase</subject><subject>Metalloproteinase</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Molecular modelling</subject><subject>Protease inhibitors</subject><subject>Radiation therapy</subject><subject>Testing</subject><subject>Toxicity</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><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><recordid>eNptkktv1DAUhSMEolXbNTtkiQ2baX3jxI8VGo2gVOqoC2Bt3STOjKvEDrYzYnb8dDxtKW2FvfDrO8c6V7co3gE9Z0zRixZda0IEDlDSUr0qjksqygXnqnr9ZH9UnMV4S_NgDAQXb4sjJqViUKnj4vdqH5PB0TpDvs3TFEyMJpLVnTVZmWEgV26H0XpH0HVkbTcB0-FkHbkcrG8GjMmPSNI2-HmzzfjWNvYO8T1ZYwr2F1mbhMPgp-CTsQ6jIcs22Z1N-9PiTY9DNGcP60nx48vn76uvi-uby6vV8nrRMsHSomoAoZXQCMkrWVOu6p5jyboaOlWiaWSveugrrDNZyoazupJSKKhQNSYnPyk-3ftOczOarjUuBRz0FOyIYa89Wv38xdmt3vidBgABIKvs8PHBIfifs4lJjza2uULojJ-jZlRQSYGVZUY_vEBv_RxczpcpLpjMLPyjNjgYbV3v88ftwVQvhRJSKVrxTJ3_h8qzM6NtvTO9zffPBBf3gjb4GIPpH0MC1YfG0S8aJyveP63NI_-3TdgfFojAeg</recordid><startdate>20240527</startdate><enddate>20240527</enddate><creator>Jung, Jinkyu</creator><creator>Celiku, Orieta</creator><creator>Rubin, Benjamin I</creator><creator>Gilbert, Mark R</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</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><orcidid>https://orcid.org/0000-0002-0500-1032</orcidid><orcidid>https://orcid.org/0000-0002-8359-6246</orcidid></search><sort><creationdate>20240527</creationdate><title>Cysteamine Suppresses Cancer Cell Invasion and Migration in Glioblastoma through Inhibition of Matrix Metalloproteinase Activity</title><author>Jung, Jinkyu ; 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Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine's inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38893149</pmid><doi>10.3390/cancers16112029</doi><orcidid>https://orcid.org/0000-0002-0500-1032</orcidid><orcidid>https://orcid.org/0000-0002-8359-6246</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Antineoplastic drugs Brain cancer Brain research Brain tumors Cancer therapies Cell death Cell growth Cell migration Chemical bonds Computational neuroscience Cysteamine Cystinosis Cytotoxicity Development and progression Drug therapy Enzymes Extracellular matrix Gelatinase A Gelatinase B Gene expression Glioblastoma Glioblastoma multiforme Glioma Health aspects Mammalian cells Matrix metalloproteinase Metalloproteinase Metastases Metastasis Molecular modelling Protease inhibitors Radiation therapy Testing Toxicity Tumors |
| title | Cysteamine Suppresses Cancer Cell Invasion and Migration in Glioblastoma through Inhibition of Matrix Metalloproteinase Activity |
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