Enhancement of sodium borocaptate (BSH) uptake by tumor cells induced by glutathione depletion and its radiobiological effect

• Published in: Cancer letters Vol. 215; no. 1; pp. 61 - 67
• Main Authors: Yoshida, Fumiyo, Matsumura, Akira, Yamamoto, Tetsuya, Kumada, Hiroaki, Nakai, Kei
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 08.11.2004; Elsevier Limited
• Subjects: Acids; Animals; Borohydrides - metabolism; Boron; Boron Neutron Capture Therapy; Brain Neoplasms - metabolism; Brain Neoplasms - radiotherapy; Buthionine sulfoximine; Buthionine Sulfoximine - pharmacology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - radiotherapy; Cells, Cultured; Cricetinae; Down-Regulation; Drug dosages; Free radicals; Gamma Rays; Gamma-irradiation; Glioma - metabolism; Glioma - radiotherapy; Glutathione; Glutathione - metabolism; Lung - cytology; Lung - drug effects; Membrane filters; Mice; Neutron; Neutrons; Radiation-Sensitizing Agents - pharmacology; Rats; Relative Biological Effectiveness; Sodium; Sodium borocaptate; Sulfhydryl Compounds - metabolism; Japan; Gamma-irradiation; Buthionine sulfoximine; Neutron; Sodium borocaptate; Glutathione
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2004.06.023

Sodium borocaptate (BSH) is widely used for boron neutron capture therapy (BNCT) of brain tumors. However, the mechanism of uptake by the tumor remains unclear. We investigated the sulfhydryl moiety of this compound. Down regulation of glutathione (GSH) by buthionine sulfoximine in cultured cells resulted in increase of BSH uptake (7.9–36.5%) compared to the control group and consequently the cytocidal effect of neutron irradiation also increased. On the other hand, the radiation caused damage by gamma-ray irradiation was suppressed when BSH uptake increased. These findings suggested that modulation of GSH enhanced the effect of B ( n, α) reaction and the protective effect of secondary gamma-ray in BNCT.