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-Sulfoquinovosylmonoacylglycerol Is a Novel Potent Radiosensitizer Targeting Tumor Angiogenesis

¹ Oral Radiation Oncology, Department of Oral Restitution, Graduate School, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo; ² Department of Applied Biological Science, Frontier Research Center for Genomic Drug Discovery, Tokyo University of Science, Yamazaki, Noda, Chiba; ³ Department of Biomedical Engineering, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo; and ⁴ Marine Biomedical Institute, Sapporo Medical University School of Medicine, Oshidomari, Rishirifuji, Hokkaido, Japan

Requests for reprints: Masahiko Miura, Oral Radiation Oncology, Department of Oral Restitution, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. Phone: 81-3-5803-5545; Fax: 81-3-5803-0205; E-mail: masa.mdth{at}tmd.ac.jp.

Angiogenesis is a promising target for the treatment of cancer, and varying types of antiangiogenic agents have been developed. However, limitations and problems associated with antiangiogenic therapy have recently arisen. Although radiotherapy can be combined with antiangiogenic compounds to overcome these difficulties, almost all previously described angiogenesis inhibitors could still cause side effects at effective doses, and only additive effects are seen in current combination therapy. In this study, we identified a member of the sulfoquinovosylacylglycerols, -sulfoquinovosylmonoacylglycerol (-SQMG), originally derived from sea urchins, as a potent radiosensitizer. The agent synergistically inhibits angiogenesis at low doses when combined with ionizing radiation. Combined treatment with -SQMG and radiation seems to promote the adoption of a senescence-like phenotype by vascular endothelial cells. Finally, the agent remarkably enhances the radioresponse of human tumors transplanted into nude mice, accompanied by a significant reduction in the vascularity of the tumors. Collectively, -SQMG may be a novel potent radiosensitizer targeting angiogenesis. (Cancer Res 2006; 66(4): 2287-95)