Inhibition of topoisomerase IIa: Novel function of wedelolactone
|Year of publication
|Article in Periodical
|Magazine / Source
|MU Faculty or unit
|Genetics and molecular biology
|Apoptosis; DNA damage; Proliferation; Topoisomerase; 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 NFkB 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 NFkB 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 IIa. We conclude that wedelolactone can act as growth suppressor independently of NFkB and androgen receptors.