{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T06:35:16Z","timestamp":1770964516376,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K10455, 23K25218, 18H02705"],"award-info":[{"award-number":["24K10455, 23K25218, 18H02705"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>5-Aminolevulinic acid (5-ALA)-based radiodynamic therapy (RDT), an experimental approach that combines systemic administration of 5-ALA with ionizing radiation, has demonstrated antitumor efficacy primarily in preclinical studies using fractionated irradiation protocols. In recent years, single-dose and hypofractionated irradiation regimens have been increasingly adopted in clinical radiotherapy; however, the therapeutic potential of 5-ALA-based RDT under single-dose irradiation conditions remains to be elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated the accumulation of protoporphyrin IX (PpIX) in human colon cancer HT-29 cells compared with previously studied cell lines, mouse melanoma B16\/BL6 and human glioblastoma U-251 MG, U-87 MG\n                      <jats:italic>in vitro<\/jats:italic>\n                      . Using a HT-29 xenograft mouse model, we investigated the antitumor efficacy of a single 12 Gy X-ray dose combined with 5-ALA at doses of 100 or 200 mg\/kg. Tumor growth, histopathological alterations, and immune cell infiltration were analyzed. Gene expression profiles of tumor tissues were examined by microarray analysis at day 29 post-irradiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HT-29 cells exhibited equal or greater PpIX accumulation compared with other tumor cell lines.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , single-dose X-ray irradiation (12 Gy) combined with various doses of 5-ALA resulted in 5-ALA dose-dependent suppression of tumor growth. Notably, administration of 200 mg\/kg 5-ALA plus 12 Gy X-ray induced marked tumor regression in all animals without statistically significant weight loss. Histopathological analysis demonstrated disruption of tumor cell islands and increased infiltration and proximity of Iba1-positive immune cells to tumor cells. Microarray analysis identified 75 differentially expressed genes between untreated and 200 mg\/kg 5-ALA plus X-ray groups, including downregulation of genes involved in DNA repair, tumor suppression, autophagy, cell cycle regulation, metabolism, and immune evasion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates for the first time that 5-ALA combined with single-dose X-ray irradiation exerts a strong antitumor effect on HT-29 xenografts. The observed effects may be mediated by induction of immunogenic cell death, modulation of the tumor microenvironment, and suppression of tumor cell survival pathways. These findings highlight single-dose 5-ALA-based RDT as a potential novel therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2025.1722919","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T05:16:30Z","timestamp":1764566190000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Antitumor efficacy of 5-aminolevulinic acid (5-ALA)-based radiodynamic therapy under single-dose X-ray irradiation in colon cancer"],"prefix":"10.3389","volume":"15","author":[{"given":"Junko","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsuke","family":"Nagasawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiupeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radphyschem.2009.06.036","article-title":"Characterization of reactive oxygen species generated by protoporphyrin IX under X-ray irradiation","volume":"78","author":"Takahashi","year":"2009","journal-title":"Radiat Phys Chem"},{"key":"B2","doi-asserted-by":"publisher","first-page":"18163","DOI":"10.1038\/s41598-019-54649-2","article-title":"Screening of X-ray responsive substances for the next generation of radiosensitizers","volume":"9","author":"Moriyama","year":"2019","journal-title":"Sci Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1186\/s13014-024-02408-7","article-title":"ALA-RDT in GBM: Protocol of the phase I\/II dose escalation trial of radiodynamic therapy with 5-aminolevulinic acid in patients with recurrent glioblastoma","volume":"19","author":"Pepper","year":"2024","journal-title":"Radiat Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-024-06049-3","article-title":"Beyond fluorescence-guided resection: 5-ALA-based glioblastoma therapies","volume":"166","author":"Stummer","year":"2024","journal-title":"Acta Neurochir (Wien)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2020.106430","article-title":"5-aminolevulinic acid radiodynamic therapy for treatment of high-grade gliomas: A systematic review","volume":"201","author":"Nordmann","year":"2021","journal-title":"Clin Neurol Neurosurg"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00066-025-02420-0","article-title":"5-aminolevulinic acid as an emerging radiosensitizer for radiodynamic therapy in solid tumors: A systematic review of available data and clinical potential","volume":"201","author":"Pepper","year":"2025","journal-title":"Strahlenther Onkol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117861","article-title":"The physicochemical and biochemical mechanisms of porphyrinoid-mediated radiodynamic therapy","volume":"296","author":"Leo","year":"2025","journal-title":"Eur J Med Chem"},{"key":"B8","unstructured":"Gliolan (5-aminolevulinic acid hydrochloride) \u2013 Summary of Product Characteristics\n          \n          \n          \n          2012"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13356","article-title":"The proton-coupled oligopeptide transporter 1 plays a major role in the intestinal permeability and absorption of 5-aminolevulinic acid","volume":"173","author":"Xie","year":"2016","journal-title":"Br J Pharmacol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.1038\/s41598-018-21152-z","article-title":"Verification of radiodynamic therapy by medical linear accelerator using a mouse melanoma tumor model","volume":"8","author":"Takahashi","year":"2018","journal-title":"Sci Rep"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22189762","article-title":"In vivo study of the efficacy and safety of 5-aminolevulinic radiodynamic therapy for glioblastoma fractionated radiotherapy","volume":"22","author":"Takahashi","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1177\/030089160208800511","article-title":"Radiation therapy combined with photofrin or 5-ALA: effect on Lewis sarcoma tumor lines implanted in mice","volume":"88","author":"Schaffer","year":"2002","journal-title":"Tumori"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2019.10198","article-title":"Radiosensitizing effect of 5-aminolevulinic acid in colorectal cancer","volume":"17","author":"Yamada","year":"2019","journal-title":"Vitro vivo. 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