Antitumor activity of Titanocene Y against freshly explanted human breast tumor cells and in xenografted MCF-7 tumors in mice.
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 micromol/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 micromol/l, well comparable to cisplatin, given at a concentration of 1.0 micromol/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.
Beckhove
Philipp
P
Deutsches Krebsforschungszentrum, Abteilung Zelluläre Immunologie, Heidelberg, Germany.
Oberschmidt
Olaf
O
Hanauske
Axel R
AR
Pampillón
Clara
C
Schirrmacher
Volker
V
Sweeney
Nigel J
NJ
Strohfeldt
Katja
K
Tacke
Matthias
M
D000362:Agar; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009924:Organ Culture Techniques; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C518838:Titanocene Y; D000362:Agar; D002945:Cisplatin