Stendel Ruediger, Stoltenburg-Didinger Gisela, Al Keikh Claudia Lotte, Wattrodt Michaela, Brock Mario
Department of Neurosurgery, Benjamin Franklin Medical Center, Free University of Berlin, Germany.
Anticancer Res. 2002 Mar-Apr;22(2A):809-14.
Although an inhibiting effect of the antibacterial substance taurolidine on several tumor cell lines was suggested in 1990, no specific research has been performed concerning its effect on brain tumor cells.
Monolayers of rat-derived C6 glioma, mouse-derived HT22 neuronal tumor, and human-derived U373 astrocytoma/glioblastoma cell lines were cultured and incubated with 1 microg/ml to 4 mg/ml of taurolidine. Neuronal and glial brain cells were obtained from rat fetuses at day 15 of gestation and incubated with taurolidine to investigate its effect on normal brain cells.
Following incubation with taurolidine, the tumor cells started to shrink and to become denser. Ultrastructurally, shrinkage of cytoplasm and condensation and marginalization of chromatin could be observed. Exposure to taurolidine at concentrations of 2.8 microg/ml to 2 mg/ml led to cell death of the evaluated tumor cell types. Results of flow cytometry suggested a fragmentation of DNA. Phosphatidylserine expression increased from 6% to 25% following exposure to taurolidine at a concentration of 25 microg/ml. Normal brain cells did not show any significant changes following incubation with taurolidine.
The characteristics identified by light and electron microscopy and the data obtained by flow cytometry indicate an apoptotic mechanism of cell death via currently unknown pathways. Taurolidine was found to have a direct and selective antineoplastic effect on glial and neuronal brain tumor cells in vitro.
尽管1990年就有人提出抗菌物质牛磺罗定对几种肿瘤细胞系有抑制作用，但尚未针对其对脑肿瘤细胞的作用进行具体研究。
培养大鼠来源的C6胶质瘤、小鼠来源的HT22神经肿瘤以及人来源的U373星形细胞瘤/胶质母细胞瘤细胞系的单层细胞，并与1微克/毫升至4毫克/毫升的牛磺罗定一起孵育。从妊娠第15天的大鼠胎儿中获取神经和胶质脑细胞，并与牛磺罗定一起孵育，以研究其对正常脑细胞的作用。
用牛磺罗定孵育后，肿瘤细胞开始收缩并变得更致密。在超微结构上，可以观察到细胞质收缩以及染色质凝聚和边缘化。暴露于浓度为2.8微克/毫升至2毫克/毫升的牛磺罗定导致所评估的肿瘤细胞类型发生细胞死亡。流式细胞术结果提示DNA片段化。暴露于浓度为25微克/毫升的牛磺罗定后，磷脂酰丝氨酸表达从6%增加到25%。正常脑细胞与牛磺罗定孵育后未显示任何显著变化。
光镜和电镜所确定的特征以及流式细胞术获得的数据表明，细胞死亡是通过目前未知的途径以凋亡机制发生的。发现牛磺罗定在体外对神经胶质和神经源性脑肿瘤细胞具有直接和选择性的抗肿瘤作用。
