{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T12:52:29Z","timestamp":1770987149787,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007354","name":"Yen Tjing Ling Medical Foundation","doi-asserted-by":"publisher","award":["CI\u2010111\u201011"],"award-info":[{"award-number":["CI\u2010111\u201011"]}],"id":[{"id":"10.13039\/501100007354","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002811","name":"Cathay General Hospital","doi-asserted-by":"publisher","award":["CGH\u2010MR\u2010A11123"],"award-info":[{"award-number":["CGH\u2010MR\u2010A11123"]}],"id":[{"id":"10.13039\/501100002811","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Glioblastoma multiforme (GBM) is a highly aggressive brain malignancy with limited treatment options. Radiotherapy (RT) is often used for treating unresectable GBM; however, the outcomes are often limited due to the radioresistance of GBM. Therefore, the discovery of potential radiosensitizers to enhance GBM responses to RT is crucial. Beta\u2010caryophyllene (BCP), a natural cannabinoid, promotes cancer apoptosis by upregulating the PPAR\u03b3 signaling pathway and can cross the blood\u2013brain barrier due to its lipophilic nature. This study aimed to evaluate the radiosensitizing potential of BCP in GBM cells. U87MG and GL261 cells and a GL261 tumor\u2010bearing model were treated with RT, BCP, or both. Treatment efficacy was assessed using the MTT assay and tumor growth tracking, and the underlying mechanisms were investigated using western blotting, immunofluorescence staining, and other analyses. BCP synergistically enhanced the efficacy of RT in cell culture, as evidenced by the combination index determined through the MTT assay. This enhancement was mediated by the BCP\u2010induced deceleration of DNA damage repair, as demonstrated by sustained \u03b3H2AX signal, upregulated PPAR\u03b3 levels, and reduced expression of pAKT, pERK, and NF\u2010\u03baB, indicating apoptosis induction and inhibition of survival pathways. BCP significantly inhibited tumor growth in GL261 tumor\u2010bearing mice with no discernible side effects. These findings indicate that BCP may serve as a potential radiosensitizer for improving RT outcomes in GBM by inhibiting DNA repair, inducing apoptosis, and suppressing anti\u2010apoptotic and survival pathways.<\/jats:p>","DOI":"10.1002\/ptr.8413","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T03:20:01Z","timestamp":1734060001000},"page":"776-788","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Beta\u2010Caryophyllene Augments Radiotherapy Efficacy in\n                    <scp>GBM<\/scp>\n                    by Modulating Cell Apoptosis and\n                    <scp>DNA<\/scp>\n                    Damage Repair via\n                    <scp>PPAR\u03b3<\/scp>\n                    and\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Pathways"],"prefix":"10.1002","volume":"39","author":[{"given":"Hui\u2010Wen","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Biomedical Imaging and Radiological Sciences National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei\u2010Chan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiology Cathay General Hospital  Taipei City Taiwan"},{"name":"School of Medicine Fu\u2010Jen Catholic University  New Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deng\u2010Yu","family":"Kuo","sequence":"additional","affiliation":[{"name":"Division of Radiation Oncology, Department of Radiology Far Eastern Memorial Hospital  New Taipei City Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4016-6753","authenticated-orcid":false,"given":"Hui\u2010Yen","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Radiological Sciences National Yang Ming Chiao Tung University  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,12,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12092511"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.584626"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520620666200227093216"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.24748"},{"issue":"6","key":"e_1_2_12_6_1","first-page":"2241","article-title":"Expression and Prognostic Significance of Kit, Protein Kinase B, and Mitogen\u2010Activated Protein Kinase in Patients With Small Cell Lung Cancer","volume":"9","author":"Blackhall F. 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