Radio-sensitization of the murine osteosarcoma cell line LM8 with parthenolide, a natural inhibitor of NF-κB

Abstract

Abstract. Nuclear factor (NF)-κB has been shown to be associated with cancer resistance to radiotherapy (RT), and is constitutively active in the murine osteosarcoma cell line, LM8. Parthenolide has been reported to show antitumor activity through inhibition of the NF-κB pathway. In this study, we investigated the radio-sensitizing activity of parthenolide. We established Luc-LM8, a stable transfectant reporter construct of NF-κB transcriptional activity into LM8. Luc-LM8 maintained the malignancy observed with LM8. In vitro, Luc-LM8 cells were cultured with or without parthenolide treatment, irradiated, and subjected to cell viability and apoptosis assays. In vivo, to investigate whether parthenolide enhances radio-sensitivity of tumors, a tumor growth assay was conducted. Parthenolide enhanced the growth inhibitory effect of RT and induced the apoptosis of Luc-LM8 cells with RT in vitro. The in vivo tumor growth was significantly suppressed in the mice treated with parthenolide and RT. The present study suggests that parthenolide sensitizes Luc-LM8 cells to irradiation. Thus, parthenolide is a potential candidate for use as a potent radio-sensitizing drug for use in cancer RT.

Traditional Medicinal Plants as a Source of Inspiration for Osteosarcoma Therapy

“…The posterior irradiation further diminished osteosarcoma cell viability [ 69 ]. Similar findings were detected in LM8 transfected with a reporter construct of NF–κB, Luc–LM8, in vitro and in vivo [ 78 ]. Importantly, synergy between parthenolide and ionizing radiation was observed against the cancer stem cells subpopulation of LM7 [ 69 ].…”

“…For these reason, radiosensitization strategies followed by a posterior chemotherapy are under investigation. It is established that the expression of NF–κB contributes to osteosarcoma radioresistance [ 70 , 78 ]. Zuch et al [ 63 ] found enhanced cell death of an aggressive derivative of Saos–2, LM7, when parthenolide and ionizing radiation were given together.…”

Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies

“…Osteosarcoma is a primary malignant bone tumor, commonly demonstrates significant radioresistance and high metastatic potential [181]. In osteosarcoma, human and murine cell line, resistance to radiotherapy has been associated with NF-κB activity [182,183]. Pretreatment with PN synergistically suppressed cell proliferation and potentiated apoptosis induced by ionizing radiation in osteosarcoma cells.…”

“…This effect was connected to the ability of PN to induce oxidative stress [182]. PN with irradiation treatment inhibited osteosarcoma tumor growth in mice more effective compared to PN or irradiation alone [183]. PN enhanced X-ray sensitivity of radiation resistant CGL1 (HeLa hybrid) cells [30].…”

Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma

“…Our system has a number of advantages, i.e. it is a fully human preclinical model, in contrast to other murine-based sarcoma cell line models 24,25,26,27 . Furthermore, whilst the confirmation of the establishment of STS primary cultures, achieved by cytomorphological, immunohistochemical and molecular cytogenetic evaluation, with the support of an experienced sarcoma pathologist, is mandatory in our protocol, this is not always the case for other STS primary culture models.…”