{"doi":"10.3390/ijms26020509","title":"Enhancing Radiation Therapy Response in Prostate Cancer Through Metabolic Modulation by Mito-Lonidamine: A 1H and 31P Magnetic Resonance Spectroscopy Study","abstract":"Radiation therapy (RT) is the cornerstone treatment for prostate cancer; however, it frequently induces gastrointestinal and genitourinary toxicities that substantially diminish the patients’ 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’s complexes I and II, emerges as a potential radiosensitizer. This study investigated Mito-LND’s 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.","journal":"International Journal of Molecular Sciences","year":2025,"id":560169,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1154980,"name":"Pradeep Kumar Gupta","orcid":"0000-0002-4036-3899","position":1,"is_corresponding":false},{"id":981052,"name":"Fernando Arias‐Mendoza","orcid":null,"position":2,"is_corresponding":false},{"id":1167153,"name":"Dinesh Kumar Singh","orcid":"0000-0002-3594-2431","position":3,"is_corresponding":false},{"id":1433293,"name":"Skyler Nova","orcid":null,"position":4,"is_corresponding":false},{"id":1154982,"name":"David Nelson","orcid":"0009-0008-5993-8710","position":5,"is_corresponding":false},{"id":230231,"name":"Vivek Narayan","orcid":"0000-0002-8205-738X","position":6,"is_corresponding":false},{"id":856869,"name":"Cameron J. Koch","orcid":null,"position":7,"is_corresponding":false},{"id":349889,"name":"Micaël Hardy","orcid":"0000-0003-2976-7785","position":8,"is_corresponding":false},{"id":479095,"name":"Ming You","orcid":"0000-0001-8683-0520","position":9,"is_corresponding":false},{"id":254811,"name":"Balaraman Kalyanaraman","orcid":"0000-0002-9180-8296","position":10,"is_corresponding":false},{"id":890594,"name":"Kavindra Nath","orcid":"0000-0002-3197-5703","position":11,"is_corresponding":false},{"id":1154981,"name":"Stepan Orlovskiy","orcid":"0009-0001-7985-6025","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:42.883572Z","pmid":"39859224","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}