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Antitumor activity of Titanocene Y against freshly explanted human breast tumor cells and in xenografted MCF-7 tumors in mice

Beckhove, Philippa; Oberschmidt, Olafb; Hanauske, Axel R.b; Pampillón, Clarac; Schirrmacher, Volkera; Sweeney, Nigel J.c; Strohfeldt, Katjac; Tacke, Matthiasc

doi: 10.1097/CAD.0b013e328010a6f7
Preclinical Reports

Bis-[(p-methoxybenzyl)cyclopentadienyl] titanium dichloride, better known as Titanocene Y, is a newly synthesized transition metal-based anticancer drug. We studied the antitumor activity of Titanocene Y with concentrations of 2.1, 21 and 210 μmol/l against a freshly explanted human breast cancer, using an in-vitro soft agar cloning system. The sensitivity against Titanocene Y was highly remarkable in the breast cancer tumor in the full concentration range. Titanocene Y showed cell death induction at 2.1 μmol/l, well comparable to cisplatin, given at a concentration of 1.0 μmol/l. A further preclinical development of Titanocene Y was warranted and therefore an MCF-7 human breast cancer xenograft nonobese diabetic/severe combined immunodeficient mouse model was used. Titanocene Y was given for 21 days at 30 mg/kg/day (75% of the maximum tolerable dose of Titanocene Y), which resulted in the reduction of the tumor volume to around one-third, whereas no mouse was lost because of the surprisingly low toxicity of Titanocene Y.

aDeutsches Krebsforschungszentrum, Abteilung Zelluläre Immunologie, Heidelberg

bAllgemeines Krankenhaus St Georg Hamburg, Hamburg, Germany

cUCD School of Chemistry and Chemical Biology, Conway Institute of Biomolecular and Biomedical Research, Centre for Synthesis and Chemical Biology (CSCB), University College Dublin, Belfield, Dublin, Ireland

Correspondence to M. Tacke, UCD School of Chemistry and Chemical Biology, Conway Institute of Biomolecular and Biomedical Research, Centre for Synthesis and Chemical Biology (CSCB), University College Dublin, Belfield, Dublin 4, Ireland

Tel: +353 1 7168428;

e-mail: matthias.tacke@ucd.ie

Sponsorship: The authors thank Science Foundation Ireland for funding through grant (04/BRG/C0682). In addition, funding from the Higher Education Authority (HEA) and the Centre for Synthesis and Chemical Biology through the HEA PRTLI cycle 3 as well as COST D39 is acknowledged.

Received 8 August 2006 Revised form accepted 8 September 2006

© 2007 Lippincott Williams & Wilkins, Inc.