Inhibition of topoisomerase IIα: Novel function of wedelolactone

The naturally occurring coumestan wedelolactone has been previously shown to reduce growth of various cancer cells. So far, the growth-suppressing effect of wedelolactone has been attributed to the inhibition of the NF kappa B transcription factor and/or androgen receptors. We found that wedelolactone suppressed growth and induced apoptosis of androgen receptor-negative MDA-MB-231 breast cancer cells at concentrations that did not inhibit the NF kappa B activity. The cells responded to wedelolactone by the S and G2/M phase cell cycle arrest and induction of the DNA damage signaling. Wedelolactone interacted with dsDNA and inhibited the activity of DNA topoisomerase II alpha. We conclude that wedelolactone can act as growth suppressor independently of NF kappa B and androgen receptors. (C) 2011 Elsevier Ireland Ltd. All rights reserved.