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

Sugiyasu,Kenjiro; Nanno,Katsuhiko; Tamai,Noriyuki; Hashimoto,Nobuyuki; Kishida,Yuki; Yoshikawa,Hideki; Myoui,Akira

doi:10.3892/ol.2011.277

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

Authors:
- Kenjiro Sugiyasu
- Katsuhiko Nanno
- Noriyuki Tamai
- Nobuyuki Hashimoto
- Yuki Kishida
- Hideki Yoshikawa
- Akira Myoui
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Affiliations: Department of Orthopaedics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Department of Orthopaedics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Department Kampo Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Medical Center for Translational Research, Osaka University Hospital, Osaka 565-0871, Japan
Published online on: March 21, 2011 https://doi.org/10.3892/ol.2011.277
Pages: 407-412

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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.

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