title: Effectiveness of sulforaphane as a radiosensitizer for murine osteosarcoma             cells.
abstract: Sulforaphane (SFN), a naturally occurring member of the isothiocyanate family,             is effective against various types of malignant tumor cells. We studied whether             the combination of SFN and radiation would be more effective against osteosarcoma             cells when compared to these treatments alone. LM8 murine osteosarcoma cells were             cultured with various concentrations of SFN for 24 h and/or 2 Gy X-irradiation.             The effects of individual and combination treatments on the number of cells, the             cell cycle, cell proliferation-related factors and apoptosis were analyzed. The             combination of SFN plus radiation had significantly greater antitumor effects             than either treatment alone. Exposure to SFN increased the population of cells             in the G2/M phase. Combination treatment resulted in a higher percentage of cells             being in sub-G1 than did SFN alone. In addition, the combination of SFN and radiation             effectively induced nuclear fragmentation and apoptotic bodies, as shown by DAPI             staining. The combination of SFN and 2 Gy radiation increased the cleavage and             activation of caspase-3 compared with SFN or radiation alone, as shown by western             blotting. Although radiation alone increased the phosphorylation of ERK and Akt             proteins, the combination of SFN and radiation induced suppression of ERK and             Akt phosphorylation when compared with radiation alone. We found that SFN enhanced             the radiosensitivity of LM8 murine osteosarcoma cells by inducing apoptosis through             G2/M-phase arrest and by inhibiting ERK and Akt activation. These findings suggest             that SFN can be used as a radiosensitizer for osteosarcomas.
authors.affiliation: Department of Orthopaedics, Graduate School of Medical Science,                     Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sawai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Murata
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Horii
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Koto
authors.forename: Takaaki
authors.initials: T
authors.lastname: Matsui
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Horie
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Tsuji
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kubo
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001859:Bone Neoplasms / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004354:Drug Screening Assays, Antitumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D051379:Mice; D012516:Osteosarcoma / Q000188:drug therapy*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000528:radiation effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013454:Sulfoxides
chemical_list: D000970:Antineoplastic Agents; D017879:Isothiocyanates; D011838:Radiation-Sensitizing Agents; D013454:Sulfoxides; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C016766:sulforaphane