Journal article
Superoxide Dismutase Mimetic Avasopasem Manganese Enhances Radiation Therapy Effectiveness in Soft Tissue Sarcomas and Accelerates Wound Healing
Antioxidants, Vol.13(5), 587
01/01/2024
DOI: 10.3390/antiox13050587
PMCID: PMC11117842
PMID: 38790692
Abstract
Soft tissue sarcomas (STSs) are mesenchymal malignant lesions that develop in soft tissues. Despite current treatments, including radiation therapy (RT) and surgery, STSs can be associated with poor patient outcomes and metastatic recurrences. Neoadjuvant radiation therapy (nRT), while effective, is often accompanied by severe postoperative wound healing complications due to damage to the surrounding normal tissues. Thus, there is a need to develop therapeutic approaches to reduce nRT toxicities. Avasopasem manganese (AVA) is a selective superoxide dismutase mimetic that protects against IR-induced oral mucositis and lung fibrosis. We tested the efficacy of AVA in enhancing RT in STSs and in promoting wound healing. Using colony formation assays and alkaline comet assays, we report that AVA selectively enhanced the STS (liposarcoma, fibrosarcoma, leiomyosarcoma, and MPNST) cellular response to radiation compared to normal dermal fibroblasts (NDFs). AVA is believed to selectively enhance radiation therapy by targeting differential hydrogen peroxide clearance in tumor cells compared to non-malignant cells. STS cells demonstrated increased catalase protein levels and activity compared to normal fibroblasts. Additionally, NDFs showed significantly higher levels of GPx1 activity compared to STSs. The depletion of glutathione using buthionine sulfoximine (BSO) sensitized the NDF cells to AVA, suggesting that GPx1 may, in part, facilitate the selective toxicity of AVA. Finally, AVA significantly accelerated wound closure in a murine model of wound healing post RT. Our data suggest that AVA may be a promising combination strategy for nRT therapy in STSs.
Details
- Title: Subtitle
- Superoxide Dismutase Mimetic Avasopasem Manganese Enhances Radiation Therapy Effectiveness in Soft Tissue Sarcomas and Accelerates Wound Healing
- Creators
- Amira Zaher - University of IowaKranti Mapuskar - University of IowaMichael Petronek - University of IowaMunir Tanas - University of IowaAlexandra Isaacson - University of IowaRebecca Dodd - University of IowaMohammed Milhem - University of IowaMuhammad Furqan - University of IowaDouglas Spitz - University of IowaBenjamin J Miller - University of IowaRobert BeardsleyBryan Allen - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Antioxidants, Vol.13(5), 587
- Publisher
- MDPI AG
- DOI
- 10.3390/antiox13050587
- PMID
- 38790692
- PMCID
- PMC11117842
- eISSN
- 2076-3921
- Language
- English
- Date published
- 01/01/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Iowa Neuroscience Institute; Orthopedics and Rehabilitation; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984628238502771
Metrics
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