Inhibition of topoisomerase IIα: novel function of wedelolactone.

Abstract

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 NFκB 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 NFκB 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 IIα. We conclude that wedelolactone can act as growth suppressor independently of NFκB and androgen receptors.

• Authors: Petr Benes, Lucia Knopfova, Filip Trcka, Alice Nemajerova, Diana Pinheiro, Karel Soucek, Miroslav Fojta, Jan Smarda
• Journal: Cancer letters (Cancer Lett) Vol. 303 Issue 1 Pg. 29-38 (Apr 01 2011) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 21315506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antigens, Neoplasm
• Antineoplastic Agents
• Coumarins
• DNA-Binding Proteins
• Topoisomerase Inhibitors
• wedelolactone
• DNA Topoisomerases, Type II

Topics

• Antigens, Neoplasm (metabolism)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, enzymology, pathology)
• Cell Cycle (drug effects)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Coumarins (pharmacology)
• DNA Damage
• DNA Topoisomerases, Type II (metabolism)
• DNA-Binding Proteins (antagonists & inhibitors, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Immunoblotting
• Signal Transduction
• Topoisomerase Inhibitors (pharmacology)