{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T22:04:21Z","timestamp":1781042661594,"version":"3.54.1"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS109423"],"award-info":[{"award-number":["NS109423"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["3R01 NS109423-02"],"award-info":[{"award-number":["3R01 NS109423-02"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA062203"],"award-info":[{"award-number":["P30CA062203"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009819","name":"Chao Family Comprehensive Cancer Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009819","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001034","name":"CHOC Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001034","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000902","name":"Pediatric Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000902","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Medulloblastoma is the most common malignant brain tumor in children. It has WNT-driven, SHH-driven\/\n                    <jats:italic>TP53<\/jats:italic>\n                    mutant, SHH-driven\/\n                    <jats:italic>TP53<\/jats:italic>\n                    wildtype, and non-WNT\/non-SHH subgroups. MAGMAS (Mitochondrial Associated Granulocyte Macrophage colony-stimulating factor Signaling molecules) encodes a mitochondrial import inner membrane translocase subunit and is responsible for the translocation of matrix proteins across the inner membrane. We previously reported that a small molecule MAGMAS inhibitor, BT9, decreases cell proliferation, migration, and oxidative phosphorylation in adult glioblastoma cell lines. The aim of our study was to investigate whether the chemotherapeutic effect of BT9 can be extended to pediatric medulloblastoma.\n                    <jats:bold>Methods:<\/jats:bold>\n                    DAOY (SHH driven\/tp53 mutant) and D425 (non-SHH group 3) were treated with BT9. For\n                    <jats:italic>in vitro<\/jats:italic>\n                    analysis, cell proliferation, death, migration, invasion, and metabolic activity were assessed using MTT assay, TUNEL staining, scratch wound assay, Matrigel invasion chambers, and seahorse assay, respectively. A D425 orthotopic xenograft mouse model was used to evaluate BT9 efficacy in\n                    <jats:italic>vivo<\/jats:italic>\n                    .\n                    <jats:bold>Results:<\/jats:bold>\n                    BT9 treatment resulted in a significant decrease in cell proliferation (DAOY, 24 hours IC50: 3.6 \u03bcM, 48 hours IC50: 2.3 \u03bcM, 72 hours IC50: 2.1 \u03bcM; D425 24 hours IC50: 3.4 \u03bcM, 48 hours IC50: 2.2 \u03bcM, 72 hours IC50: 2.1 \u03bcM) and a significant increase in cell death (DAOY, 24 hours p = 0.0004, 48 hours p&lt;0.0001; D425, 24 hours p = 0.0001, 48 hours p = 0.02). In DAOY cells, 3 \u03bcM BT9 delayed migration and significantly reduced DAOY and D425 cell invasion (p &lt; 0.0001). It also modified mitochondrial respiratory function in both medulloblastoma cell lines. Compared to control, however, BT9 administration did not improve survival in a D425 orthotopic xenograft mouse model.\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    Our\n                    <jats:italic>in vitro<\/jats:italic>\n                    data showed BT9 antitumor efficacy in DAOY and D425 cell lines, suggesting that BT9 may represent a promising targeted therapeutic in pediatric medulloblastoma. These data, however, need to be further validated in animal models.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0300411","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T13:34:58Z","timestamp":1729604098000},"page":"e0300411","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Preclinical assessment of MAGMAS inhibitor as a potential therapy for pediatric medulloblastoma"],"prefix":"10.1371","volume":"19","author":[{"given":"Zahra","family":"Motahari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8956-6999","authenticated-orcid":true,"given":"Javier J.","family":"Lepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malia 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