{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:56:59Z","timestamp":1791244619223,"version":"4.1.0"},"reference-count":55,"publisher":"Radiation Research Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2025,2,12]]},"abstract":"<jats:p>Breast cancer is a commonly diagnosed cancer, while resistance to radiation therapy remains an important factor hindering the treatment of patients. Timosaponin AIII (Tim AIII) is a steroidal saponin from the Anemarrhena asphodeloides. Its pharmacologic effects and mechanisms for enhancing radiotherapy remain largely unknown. This study investigates Tim AIII and aims to unravel the underlying mechanisms. Experiments, including cell cloning, scratch assays, cell cycle, apoptosis assays, immunofluorescence staining, and reactive oxygen species (ROS) assessments, were conducted on breast cancer cell lines MDA-MB-231 and JIMT-1 to investigate the impact of Tim AIII combined with radiation. Western blot analyses were used to detect \u03b3-H2AX expression, ROS-related pathways, ATM-CHK2, and AKT-MTOR pathways. Subcutaneous tumor experiments in nude mice confirmed in vivo radiation sensitization. When combined with radiation, Tim AIII significantly inhibited cell clone formation, impeded cancer cell migration, increased G2\/M phase arrest and apoptosis. Immunofluorescence showed prolonged \u03b3-H2AX signals. Molecular investigations indicated Tim AIII amplified radiation-induced ROS production, inducing ROS-mediated DNA damage and apoptosis. It activated ATM-CHK2 while inhibiting the AKT-MTOR pathway. Tim AIII enhances radiation sensitivity in breast cancer cells, both in vitro and in vivo. Through ROS-mediated DNA damage and apoptosis, activation of ATM\/Chk2 and inhibition of the AKT-MTOR pathway induce G2\/M phase arrest, ultimately boosting radiation sensitivity via the mitochondrial-mediated apoptotic pathway.<\/jats:p>","DOI":"10.1667\/rade-24-00087.1","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T19:01:33Z","timestamp":1739300493000},"page":"257-270","source":"Crossref","is-referenced-by-count":3,"title":["Timosaponin AIII Enhances Radiosensitivity in Breast Cancer through Induction of ROS-Mediated DNA Damage and Apoptosis"],"prefix":"10.1667","volume":"203","author":[{"given":"Huiting","family":"Peng","sequence":"first","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqing","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Science, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yuan","sequence":"additional","affiliation":[{"name":"Shandong Academy of Traditional Chinese Medicine, Jinan 250014, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Shi","sequence":"additional","affiliation":[{"name":"Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguo","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"H Sung, J Ferlay, R L Siegel,  \"CA Cancer J Clin.\"  71, \"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.\" 209 (2021)","DOI":"10.3322\/caac.21660"},{"key":"2","doi-asserted-by":"crossref","unstructured":"R Dent, M Trudeau, K I Pritchard,  \"Clin Cancer Res.\"  13, \"Triple-negative breast cancer: clinical features and patterns of recurrence.\" 4429 (2007)","DOI":"10.1158\/1078-0432.CCR-06-3045"},{"key":"3","doi-asserted-by":"crossref","unstructured":"C M Perou, T S\u00f8rlie, M B Eisen,  \"Nature.\"  406, \"Molecular portraits of human breast tumours.\" 747 (2000)","DOI":"10.1038\/35021093"},{"key":"4","doi-asserted-by":"crossref","unstructured":"A Recht, E A Comen, R E Fine,  \"J Clin Oncol.\"  34, \"Postmastectomy Radiotherapy: An american society of clinical 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