title: Targeting radioresistant osteosarcoma cells with parthenolide.
abstract: Osteosarcoma is a devastating tumor of bone, primarily affecting adolescents. Osteosarcoma tumors are notoriously radioresistant. Radioresistant cancers, including osteosarcoma, typically exhibit a considerable potential for relapse and development of metastases following treatment. Relapse and metastatic potential can, in part, be due to a specific radioresistant subpopulation of cells with stem-like characteristics, cancer stem cells, which maintain the capacity to regenerate entire tumors. In the current study, we have investigated whether in vitro treatments with parthenolide, a naturally occurring small molecule that interferes with NF-κB signaling and has various other effects, will re-sensitize cancer stem cells and the entire cell population to radiotherapy in osteosarcoma. Our results indicate that parthenolide and ionizing radiation synergistically induce cell death in LM7 osteosarcoma cells. Importantly, the combination treatment results in a significant reduction in the viability of both the overall population of osteosarcoma cells and the cancer stem cell subpopulation. This effect is dependent on the ability of parthenolide to induce oxidative stress. Therefore, as a supplement to current multimodal therapy, parthenolide may sensitize osteosarcoma tumors to radiation and greatly reduce the prevalence of relapse and metastatic progression.
authors: Center for Musculoskeletal Research, University of Rochester School of Medicine & Dentistry, 575 Elmwood Ave., Rochester, New York 14642, USA.
authors: Daniel
authors: D
authors: Zuch
authors: An-Hoa
authors: AH
authors: Giang
authors: Yuriy
authors: Y
authors: Shapovalov
authors: Edward
authors: E
authors: Schwarz
authors: Randy
authors: R
authors: Rosier
authors: Regis
authors: R
authors: O'Keefe
authors: Roman A
authors: RA
authors: Eliseev
mesh_terms: D015153:Blotting, Western; D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000528:radiation effects; D012516:Osteosarcoma / Q000473:pathology*; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C002669:parthenolide