Walters Denise K, Muff Roman, Langsam Bettina, Gruber Philipp, Born Walter, Fuchs Bruno
Laboratory for Orthopaedic Research, Department of Orthopaedics, Balgrist University Hospital, University of Zurich, Forchstrasse 340, 8008 Zürich, Switzerland.
Invest New Drugs. 2007 Aug;25(4):305-12. doi: 10.1007/s10637-007-9052-9. Epub 2007 Apr 26.
Taurolidine, the active agent of Taurolin, is a broad spectrum anti-biotic that has been used for over 15 years for the treatment of severe surgical infections. Recently, taurolidine has been shown to possess anti-neoplastic properties in vitro and in vivo against a variety of cancers including ovarian, colon and prostate. In this study we assessed the cytotoxic activity of taurolidine against human osteosarcoma (OS) cell lines and normal human bone cells. Treatment with taurolidine inhibited the growth of all ten osteosarcoma cell lines tested and taurolidine was equally potent against cell lines with and without distinct genetic defects (i.e. p53, Rb). Moreover, taurolidine-induced growth inhibition was found to be associated with a dose dependent increase in the number of apoptotic cells and apoptosis was shown to be caspase-dependent. Taurolidine treatment was also found to inhibit adhesion of OS cell lines. Compared to OS cell lines, normal bone cells in primary culture were found to be less sensitive to the cytotoxic and anti-adhesive effects of taurolidine. These data indicate that taurolidine possesses potent anti-neoplastic activity against osteosarcoma cell lines and may have potential as a novel OS chemotherapeutic agent.
牛磺罗定是牛磺罗宁的活性成分,是一种广谱抗生素,已用于治疗严重外科感染超过15年。最近,牛磺罗定已被证明在体外和体内对包括卵巢癌、结肠癌和前列腺癌在内的多种癌症具有抗肿瘤特性。在本研究中,我们评估了牛磺罗定对人骨肉瘤(OS)细胞系和正常人骨细胞的细胞毒活性。用牛磺罗定处理可抑制所测试的所有十种骨肉瘤细胞系的生长,并且牛磺罗定对具有和不具有明显遗传缺陷(即p53、Rb)的细胞系同样有效。此外,发现牛磺罗定诱导的生长抑制与凋亡细胞数量的剂量依赖性增加有关,并且凋亡显示为半胱天冬酶依赖性。还发现牛磺罗定处理可抑制OS细胞系的粘附。与OS细胞系相比,原代培养的正常骨细胞对牛磺罗定的细胞毒和抗粘附作用较不敏感。这些数据表明牛磺罗定对骨肉瘤细胞系具有强大的抗肿瘤活性,并且可能具有作为新型OS化疗药物的潜力。