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: Yasushi Sawai, Hiroaki Murata, Motoyuki Horii, Kazutaka Koto, Takaaki Matsui, Naoyuki Horie, Yoshiro Tsuji, Eishi Ashihara, Taira Maekawa, Toshikazu Kubo, Shinji Fushiki
• Journal: Oncology reports (Oncol Rep) Vol. 29 Issue 3 Pg. 941-5 (Mar 2013) ISSN: 1791-2431 [Electronic] Greece
• PMID: 23254561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Isothiocyanates
• Radiation-Sensitizing Agents
• Sulfoxides
• Proto-Oncogene Proteins c-akt
• Extracellular Signal-Regulated MAP Kinases
• sulforaphane

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects, radiation effects)
• Bone Neoplasms (drug therapy)
• Cell Cycle Checkpoints (drug effects, radiation effects)
• Cell Line, Tumor (drug effects)
• Cell Survival (drug effects, radiation effects)
• Drug Screening Assays, Antitumor
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Isothiocyanates (pharmacology)
• Mice
• Osteosarcoma (drug therapy)
• Phosphorylation
• Protein Processing, Post-Translational (drug effects, radiation effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Radiation-Sensitizing Agents (pharmacology)
• Sulfoxides