Antitumor activity of vanadocene Y and its selenocyanate derivative in xenografted caki-1 tumors in mice

作者：Fichtner Iduna; Claffey James; Deally Anthony; Gleeson Brendan; Hogan Megan; Markelova Maria Rivera; Mueller Bunz Helge; Weber Holger; Tacke Matthias^*

来源：Journal of Organometallic Chemistry, 2010, 695(8): 1175-1181.

DOI：10.1016/j.jorganchem.2010.01.026

• Anticancer drug
• Vanadocene dichloride
• Renal-cell cancer
• Cytotoxicity
• Xenograft
• Anti-angiogenesis

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 mu M (1) and 37 +/- 11 mu M (2). In a cytotoxicity assay against the human renal cancer cells, CAKI-1, the compounds demonstrated IC50 values of 0.55 +/- 0.09 mu M (1) and 0.25 +/- 0.03 mu M (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.

• 出版日期2010-4-15