Targeting radioresistant osteosarcoma cells with parthenolide

Daniel Zuch, An Hoa Giang, Yuriy Shapovalov, Edward Schwarz, Randy Rosier, Regis O'Keefe, Roman A. Eliseev

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish
Pages (from-to)1282-1291
Number of pages10
JournalJournal of cellular biochemistry
Volume113
Issue number4
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

Keywords

  • CANCER STEM CELLS
  • NF-κB
  • OSTEOSARCOMA
  • PARTHENOLIDE
  • RADIATION
  • ROS

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    Zuch, D., Giang, A. H., Shapovalov, Y., Schwarz, E., Rosier, R., O'Keefe, R., & Eliseev, R. A. (2012). Targeting radioresistant osteosarcoma cells with parthenolide. Journal of cellular biochemistry, 113(4), 1282-1291. https://doi.org/10.1002/jcb.24002