Buthionine sulphoximine alone and in combination with melphalan (L-PAM) is highly cytotoxic for human neuroblastoma cell lines
Buthionine sulphoximine alone and in combination with melphalan (L-PAM) is highly cytotoxic for human neuroblastoma cell lines
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DOI：
10.1016/s0959-8049(97)00203-7
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发表时间：
1997-10-01
影响因子：
8.4
通讯作者：
Reynolds, CP
中科院分区：
文献类型：
--
作者：
Anderson, CP;Tsai, J;Reynolds, CP
丁硫氨酸亚砜（BSO）选择性抑制谷胱甘肽（GSH）的合成，并可能增强melphalan （L-PAM）抗神经母细胞瘤的活性。我们测定了BSO（剂量范围0-1000 μ M）单独使用和与L-PAM（剂量范围0-0 μ M）联合使用对18个人神经母细胞瘤细胞系的细胞毒性。单独BSO对16/18的神经母细胞瘤细胞系具有高度的细胞毒性，其IC90值（范围2.1- 1000 μ M）低于临床可达到的500 μ M BSO稳态血浆水平。与谷胱甘肽水平相关的最大细胞杀伤下降到低于基线的10%，并且通过添加外源性抗氧化剂（谷胱甘肽、维生素E和抗坏血酸）部分逆转。用隧道法对DNA片段进行荧光细胞分析，发现在500 μ M BSO作用48小时后，92%的BSO敏感细胞系发生凋亡。L-PAM与BSO联用可通过>1-3 log（联合指数）协同增强L-PAM单用对细胞的杀伤作用
Buthionine sulphoximine (BSO) selectively inhibits glutathione (GSH) synthesis and may enhance the antineuroblastoma activity of melphalan (L-PAM). We determined the cytotoxicity of BSO (dose range 0-1000 mu M) alone and in combination with L-PAM (dose range 0-0 mu M) in a panel of 18 human neuroblastoma cell lines. BSO alone was highly cytotoxic with 16/18 neuroblastoma cell lines having IC90 values (range 2.1->1000 mu M) below the clinically achievable steady-state plasma level of 500 mu M BSO. Maximal cell killing correlated with GSH levels decreased to less than 10% baseline, and was partially reversed by the addition of exogenous anti-oxidants (GSH, vitamin E and ascorbate). Fluorocytometric analysis of DNA fragments by the Tunnel method detected 92% of a BSO-sensitive cell line in apoptosis after a 48 h exposure to 500 mu M BSO. The combination of L-PAM and BSO synergistically enhanced the cell killing of L-PAM alone by >1-3 logs (combination index