Antitumor activity of vanadocene Y and its selenocyanate derivative in xenografted caki-1 tumors in mice |
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Authors: | Iduna Fichtner,Anthony Deally,Megan Hogan,Helge Mü ller-Bunz,Matthias Tacke |
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Affiliation: | a Max Delbrück Center (MDC) for Molecular Medicine, Robert-Rössle-Str. 10, D-13125, Berlin, Germany b Experimental Pharmacology and Oncology (EPO) GmbH, Robert-Rössle-Str. 10, D-13125, Berlin, Germany c UCD School of Chemistry and Chemical Biology, Centre for Synthesis and Chemical Biology (CSCB), Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland d ProQinase GmbH Freiburg, Breisacher Str. 117, D-79106 Freiburg, Germany |
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Abstract: | The para-methoxybenzyl-substituted vanadocene dichloride (Vanadocene Y) (1) and its diselenocyanate (Selenocyanato-Vanadocene Y) (2) were tested in vitro in an anti-angiogenesis assay against human umbilical vein endothelial cells (HUVEC) delivering IC50 values of 0.92 ± 0.03 μM (1) and 37 ± 11 μM (2). In a cytotoxicity assay against the human renal cancer cells, CAKI-1, the compounds demonstrated IC50 values of 0.55 ± 0.09 μM (1) and 0.25 ± 0.03 μM (2). Then both compounds were given at their maximum tolerable dose, MTD, of 20 mg/kg/d (1) or 40 mg/kg/d (2) on four consecutive days or at 50% of the MTD on five consecutive days per week for three weeks to overall four cohorts of eight CAKI-1 tumor-bearing female NMRI:nu/nu mice each, while a further cohort was treated with solvent only. Both MTD-treated mouse cohorts showed a statistically significant tumor growth reduction with respect to the solvent-treated control group with an optimal T/C value of 47% on day 39 of the experiment. Immunohistological analysis revealed that the expression of the proliferation marker Ki-67 was reduced due to long-term treatment with 2. |
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Keywords: | Anticancer drug Vanadocene dichloride Renal-cell cancer Cytotoxicity Xenograft Anti-angiogenesis |
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