title: Radio-sensitization of the murine osteosarcoma cell line LM8 with parthenolide, a natural inhibitor of NF-κB.
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.
authors.affiliation: Department of Orthopaedics, Osaka University Graduate School of Medicine, Osaka University Hospital, Suita, Osaka 565-0871, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Sugiyasu
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nanno
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tamai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kishida
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Myoui