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Sun, BS, Wang, JH, Liu, LL, Gong, SH, Redmond, HP;
Journal of Surgical Oncology
Taurolidine Induces Apoptosis of Murine Melanoma Cells In Vitro and In Vivo By Modulation of The Bcl-2 Family Proteins
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Background: This study evaluates whether taurolidine, a novel antibiotic agent, induces murine melanoma cell apoptosis in vitro and in vivo.. Methods: Murine melanoma cells (1316 4A5 and B16 F10) were treated with taurolidine (0-100 mu M) for 12 and 24 hr. Cell viability and apoptosis were assessed by MTT assay and FACScan analysis. Expression of the Bcl-2 family proteins was detected by Western blot analysis. In vivo, taurolidine-induced anti-tumor cytotoxicity was assessed in C57BL/6 mice. Therapeutic effectiveness, by intraperitoneal injection of taurolidine (15 mg/mouse) on alternate days for 2 weeks, was evaluated in mice bearing B16 4A5 tumor xenografts. Primary and metastatic tumor growth and intra-tumor apoptotic index were measured.. Results: Taurolidine induced cell apoptosis and reduced cell viability in murine melanoma cells. The pro-apoptotic protein Bax was enhanced, whereas the anti-apoptotic protein Bcl-2 was inhibited by taurolidine treatment. In vivo, systemic injection of 15-mg taurolidine was identified as the maximally tolerated dose. Administration of taurolidine at 15 mg/mouse significantly inhibited primary and metastatic tumor growth, which was mirrored by a significantly increased intra-tumor apoptotic index.. Conclusions: These results demonstrate that taurolidine significantly attenuated melanoma tumor growth, which may result from taurolidine-induced apoptosis by modulation of the Bcl-2 family proteins..
DOI 10.1002/jso.20827
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