{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T23:42:11Z","timestamp":1763509331923,"version":"3.45.0"},"reference-count":18,"publisher":"Georg Thieme Verlag KG","issue":"09","funder":[{"DOI":"10.13039\/501100004366","name":"Tabriz University of Medical Sciences","doi-asserted-by":"crossref","award":["67064"],"award-info":[{"award-number":["67064"]}],"id":[{"id":"10.13039\/501100004366","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Previously, diosgenin, a steroidal saponin, has demonstrated therapeutic potential for osteosarcoma. However, the underlying mechanisms still remain unknown.<\/jats:p>\n                  <jats:p>This study was designed to investigate the impact of diosgenin on methotrexate-mediated apoptosis in Saos-2 cells, specifically related to DNA damage.<\/jats:p>\n                  <jats:p>To assess the cell vitality of Saos-2 cells, we treated them with methotrexate, diosgenin, and a mixture of both, then performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide technique. Western blot was used to evaluate DNA damage by measuring the expression of \u03b3-H2AX protein. The ELISA method was also applied to find the quantity of 8-oxo-2\u2032-deoxyguanosine, and flow cytometry was used to analyze apoptosis.<\/jats:p>\n                  <jats:p>Combining methotrexate with diosgenin led to a major reduction in cell proliferation rate compared to monotreatments (p&lt;0.05). This combination significantly increased apoptosis, measured by flow cytometry, and increased levels of \u03b3-H2AX protein and 8-oxo-2\u2032-deoxyguanosine.<\/jats:p>\n                  <jats:p>Diosgenin significantly augmented methotrexate-mediated apoptosis in Saos-2 cells through enhanced DNA damage mechanisms. These findings suggest that diosgenin could serve as a promising adjuvant therapeutic agent to improve the efficacy of current methotrexate-based chemotherapy regimens in osteosarcoma treatment, potentially reducing required drug doses and minimizing associated toxicity while maintaining therapeutic effectiveness.<\/jats:p>","DOI":"10.1055\/a-2713-0136","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T23:37:43Z","timestamp":1763509063000},"page":"386-391","source":"Crossref","is-referenced-by-count":0,"title":["Diosgenin Enhances the Sensitivity to Methotrexate Through Oxidative DNA Damage in Saos-2 Osteosarcoma Cancer Cells"],"prefix":"10.1055","volume":"75","author":[{"given":"Hadi","family":"Ghobadi","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7852-8118","authenticated-orcid":false,"given":"Amir","family":"Valizadeh","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of)"},{"name":"Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4455-7858","authenticated-orcid":false,"given":"Mohsen","family":"Dashti","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of)"},{"name":"Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afsaneh","family":"Ghasemzadeh","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of)"},{"name":"Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4220-1527","authenticated-orcid":false,"given":"Bahman","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry and Laboratory Medicine, Tabriz University of Medical Sciences, Tabriz, Iran (the Islamic Republic of)"},{"name":"Department of Orthopedic Surgery, School of Medicine and Shohada Educational Hospital, Tabriz University of Medical Sciences Tabriz, Iran (the Islamic Republic of)"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"issue":"08","key":"ref1","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.3390\/cancers12082130","article-title":"Molecular Biology of Osteosarcoma","volume":"12","author":"A M Czarnecka","year":"2020","journal-title":"Cancers (Basel)"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"e28352","DOI":"10.1002\/pbc.28352","article-title":"Osteosarcoma","author":"B R Eaton","year":"2021","journal-title":"Pediatr Blood Cancer"},{"issue":"22","key":"ref3","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1056\/NEJMra2103423","article-title":"New horizons in the treatment of osteosarcoma","volume":"385","author":"P S Meltzer","year":"2021","journal-title":"N Engl J Med"},{"issue":"10","key":"ref4","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41571-021-00519-8","article-title":"Advancing therapy for osteosarcoma","volume":"18","author":"J Gill","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"issue":"06","key":"ref5","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1055\/a-2567-9916","article-title":"Enhancing Doxorubicin Sensitivity in Osteosarcoma Cancer Cells: Unveiling the Role of Resveratrol-Induced Oxidative DNA Damage","volume":"75","author":"M R Bazavar","year":"2025","journal-title":"Drug Res"},{"issue":"11","key":"ref6","doi-asserted-by":"crossref","first-page":"153176","DOI":"10.1016\/j.prp.2020.153176","article-title":"miR-192 enhances sensitivity of methotrexate drug to MG-63 osteosarcoma cancer cells","volume":"216","author":"M Bazavar","year":"2020","journal-title":"Pathol Res Pract"},{"issue":"19","key":"ref7","doi-asserted-by":"crossref","first-page":"e15582","DOI":"10.1097\/MD.0000000000015582","article-title":"Methotrexate, doxorubicin, and cisplatinum regimen is still the preferred option for osteosarcoma chemotherapy: A meta-analysis and clinical observation","volume":"98","author":"D Yu","year":"2019","journal-title":"Medicine (Baltimore)"},{"issue":"11","key":"ref8","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1200\/JCO.2004.11.022","article-title":"Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer","volume":"22","author":"D H Johnson","year":"2004","journal-title":"J Clin Oncol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1200\/JCO.2004.07.215","article-title":"Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2","volume":"22","author":"R Herbst","year":"2004","journal-title":"J Clin Oncol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"4156293","DOI":"10.1155\/2016\/4156293","article-title":"Diosgenin: recent highlights on pharmacology and analytical methodology","volume":"2016","author":"M Jesus","year":"2016","journal-title":"J Anal Methods Chem"},{"key":"ref11","first-page":"24","article-title":"An update on the biological and pharmacological activities of diosgenin","volume":"17","author":"J K Kim","year":"2018","journal-title":"EXCLI J"},{"issue":"10","key":"ref12","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc3599","article-title":"Cancer drug resistance: an evolving paradigm","volume":"13","author":"C Holohan","year":"2013","journal-title":"Nat Rev Cancer"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1093\/jnci\/djk015","article-title":"Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup","volume":"99","author":"I J Lewis","year":"2007","journal-title":"J Nat Cancer 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