Inhibition of DNA topoisomerases I and II, and growth inhibition of breast cancer MCF-7 cells by ouabain, digoxin and proscillaridin A.

Article Details

Citation
Copy to clipboard

Bielawski K, Winnicka K, Bielawska A

Inhibition of DNA topoisomerases I and II, and growth inhibition of breast cancer MCF-7 cells by ouabain, digoxin and proscillaridin A.

Biol Pharm Bull. 2006 Jul;29(7):1493-7.

PubMed ID
16819197 [ View in PubMed
]
Abstract

We evaluated the cytotoxicity and underlying mechanisms of cardiac glycosides, including digoxin, ouabain and proscillaridin A, on the proliferation of breast cancer MCF-7 cells. In terms of inhibition of cell proliferation of MCF-7 cells, the compounds rank in the order proscillaridin A>digoxin>ouabain. While both digoxin and ouabain inhibited topoisomerase II catalytic activity at nanomolar concentrations (100 nM), neither agent inhibited topoisomerase I catalytic activity even at concentrations as high as 100 microM. On the other hand, proscillaridin A was a potent poison of topoisomerase I and II activity at nanomolar drug concentrations (30 nM, 100 nM, respectively), suggesting that this agent may produce its cytotoxic activity by targeting both enzymes simultaneously. These studies suggest that the stabilization of DNA-topoisomerase II complexes is closely linked to the mechanism of digoxin, ouabain and proscillaridin A cytotoxicity. The potential DNA-binding properties of the cardiac glycosides have been assessed by measuring the displacement of ethidium bromide from calf thymus DNA. These results indicate that digoxin, ouabain and proscillaridin A neither intercalate nor interact with the minor groove of DNA.

DrugBank Data that Cites this Article

Drugs