Vanadocenes as potent anti-proliferative agents disrupting mitotic spindle formation in cancer cells

Anti-cancer Drugs
C S NavaraFatih M Uckun

Abstract

We present experimental data which establish the organometallic compounds vanadocene dichloride (VDC) and vanadocene acetylacetonate (VDacac) as potent anti-proliferative agents. We first examined the effects of VDC and VDacac on the rapid embryonic cell division and development of Zebrafish. Both compounds were capable of causing cell division block at the 8-16 cell stage of embryonic development followed by total cell fusion and developmental arrest. We next examined the effect of VDC and VDacac on proliferation of human breast cancer and glioblastoma cell lines using MTT assays. VDC inhibited the proliferation of the breast cancer cell line BT-20 as well as the glioblastoma cell line U373 in a concentration-dependent fashion with IC50 values of 11.0, 14.9 and 18.6 microM, respectively. VDacac inhibited cellular proliferation with IC50 values of 9.1, 26.9 and 35.5 microM, respectively. Whereas in vehicle-treated control cancer cells mitotic spindles were organized as a bipolar microtubule array and the DNA was organized on a metaphase plate, vanadocene-treated cancer cells had aberrant monopolar mitotic structures where microtubules were detected only on one side of the chromosomes and the chromosomes were arranged in a circu...Continue Reading

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Citations

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