{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T10:08:14Z","timestamp":1787998094145,"version":"build-2784847793"},"reference-count":48,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute for Translational Medicine and Therapeutics","award":["ITMAT-UL1TR001878"],"award-info":[{"award-number":["ITMAT-UL1TR001878"]}]},{"name":"Institute for Translational Medicine and Therapeutics","award":["R01CA250102"],"award-info":[{"award-number":["R01CA250102"]}]},{"name":"Institute for Translational Medicine and Therapeutics","award":["R01CA228457"],"award-info":[{"award-number":["R01CA228457"]}]},{"name":"Institute for Translational Medicine and Therapeutics","award":["R01CA268601"],"award-info":[{"award-number":["R01CA268601"]}]},{"name":"Institute for Translational Medicine and Therapeutics","award":["R21CA280523"],"award-info":[{"award-number":["R21CA280523"]}]},{"name":"NIH","award":["ITMAT-UL1TR001878"],"award-info":[{"award-number":["ITMAT-UL1TR001878"]}]},{"name":"NIH","award":["R01CA250102"],"award-info":[{"award-number":["R01CA250102"]}]},{"name":"NIH","award":["R01CA228457"],"award-info":[{"award-number":["R01CA228457"]}]},{"name":"NIH","award":["R01CA268601"],"award-info":[{"award-number":["R01CA268601"]}]},{"name":"NIH","award":["R21CA280523"],"award-info":[{"award-number":["R21CA280523"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Radiation therapy (RT) is the cornerstone treatment for prostate cancer; however, it frequently induces gastrointestinal and genitourinary toxicities that substantially diminish the patients\u2019 quality of life. While many individuals experience transient side effects, a subset endures persistent, long-term complications. A promising strategy to mitigate these toxicities involves enhancing tumor radiosensitivity, potentially allowing for lower radiation doses. In this context, mito-lonidamine (Mito-LND), an antineoplastic agent targeting the mitochondrial electron transport chain\u2019s complexes I and II, emerges as a potential radiosensitizer. This study investigated Mito-LND\u2019s capacity to augment RT efficacy and reduce adverse effects through comprehensive in vitro and in vivo assessments using hormone-sensitive and hormone-refractory prostate cancer models. Employing a Seahorse analysis and 1H\/31P magnetic resonance spectroscopy (MRS), we observed that Mito-LND selectively suppressed lactate production, decreased intracellular pH, and reduced bioenergetics and oxygen consumption levels within tumor cells. These findings suggest that Mito-LND remodels the tumor microenvironment by inducing acidification, metabolic de-energization, and enhanced oxygenation, thereby sensitizing tumors to RT. Our results underscore the potential of Mito-LND as a therapeutic adjunct in RT to improve patient outcomes and reduce radiation-associated toxicities in early-stage prostate cancer.<\/jats:p>","DOI":"10.3390\/ijms26020509","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T07:00:47Z","timestamp":1736406047000},"page":"509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Enhancing Radiation Therapy Response in Prostate Cancer Through Metabolic Modulation by Mito-Lonidamine: A 1H and 31P Magnetic Resonance Spectroscopy Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7985-6025","authenticated-orcid":false,"given":"Stepan","family":"Orlovskiy","sequence":"first","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4036-3899","authenticated-orcid":false,"given":"Pradeep Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Arias-Mendoza","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Advanced Imaging Research Inc., Cleveland, OH 44114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh Kumar","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skyler","family":"Nova","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5993-8710","authenticated-orcid":false,"given":"David S.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-738X","authenticated-orcid":false,"given":"Vivek","family":"Narayan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron J.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2976-7785","authenticated-orcid":false,"given":"Micael","family":"Hardy","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Chimie, Aix-Marseille University, CNRS, ICR, UMR 7273, 13013 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8683-0520","authenticated-orcid":false,"given":"Ming","family":"You","sequence":"additional","affiliation":[{"name":"Center for Cancer Prevention, Houston Methodist Cancer Center, Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9180-8296","authenticated-orcid":false,"given":"Balaraman","family":"Kalyanaraman","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3197-5703","authenticated-orcid":false,"given":"Kavindra","family":"Nath","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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