Taurolidine induces apoptosis of murine melanoma cells in vitro and in vivo by modulation of the Bcl-2 family proteins

✍ Scribed by Bao Sheng Sun; Jiang Huai Wang; Lin Lin Liu; Shou Liang Gong; H. Paul Redmond

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 205 KB
• Volume: 96
• Category: Article
• ISSN: 0022-4790
• DOI: 10.1002/jso.20827

✦ Synopsis

Abstract

Background

This study evaluates whether taurolidine, a novel antibiotic agent, induces murine melanoma cell apoptosis in vitro and in vivo.

Methods

Murine melanoma cells (B16 4A5 and B16 F10) were treated with taurolidine (0–100 µM) 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. J. Surg. Oncol. 2007;96: 241–248. © 2007 Wiley‐Liss, Inc.