Stendel Ruediger, Biefer Hector Rodriguez Cetina, Dékány Gabriela Marta, Kubota Hisashi, Münz Christian, Wang Sheng, Mohler Hanns, Yonekawa Yasuhiro, Frei Karl
Department of Neurosurgery, Charité-University Medicine Berlin, Berlin, Germany.
Autophagy. 2009 Feb;5(2):194-210. doi: 10.4161/auto.5.2.7404. Epub 2009 Feb 13.
The antibacterial amino-acid derivative taurolidine (TAU) has been recently shown to exhibit anti-neoplastic activity based on a mechanism, which is still unknown in detail. Cytotoxicity and clonogenic assays were performed and the impact of apoptosis modulators, a radical scavenger, autophagy inhibitors, silencing of apoptosis inducing actor (AIF) and cytochrome-c (Cyt-C) by siRNA, and knockdown of autophagy related genes were evaluated in vitro. The intracellular ATP-content, release of AIF and Cyt-C, and DNA-laddering were investigated. This study could demonstrate cell killing, inhibition of proliferation, and inhibition or prevention of colony formation in human glioma cell lines and ex vivo glioblastoma cells after incubation with TAU. This effect is based on the induction of a mixed type of programmed cell death with the main preference of autophagy, and involvement of senescence, necroptosis and necrosis. This mechanism of action may open a new approach for therapeutic intervention.
抗菌氨基酸衍生物牛磺罗定（TAU）最近被证明具有抗肿瘤活性，但其作用机制仍不清楚。进行了细胞毒性和克隆形成试验，并在体外评估了凋亡调节剂、自由基清除剂、自噬抑制剂、小干扰RNA（siRNA）沉默凋亡诱导因子（AIF）和细胞色素C（Cyt-C）以及自噬相关基因敲低的影响。研究了细胞内三磷酸腺苷（ATP）含量、AIF和Cyt-C的释放以及DNA梯状条带。本研究表明，用TAU孵育后人胶质瘤细胞系和离体胶质母细胞瘤细胞可出现细胞杀伤、增殖抑制以及集落形成抑制或预防。这种作用基于诱导一种以自噬为主的混合型程序性细胞死亡，并涉及衰老、坏死性凋亡和坏死。这种作用机制可能为治疗干预开辟一条新途径。
