title: 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.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, Czech Republic. pbenes@sci.muni.cz
authors.forename: Petr
authors.initials: P
authors.lastname: Benes
authors.forename: Lucia
authors.initials: L
authors.lastname: Knopfova
authors.forename: Filip
authors.initials: F
authors.lastname: Trcka
authors.forename: Alice
authors.initials: A
authors.lastname: Nemajerova
authors.forename: Diana
authors.initials: D
authors.lastname: Pinheiro
authors.forename: Karel
authors.initials: K
authors.lastname: Soucek
authors.forename: Miroslav
authors.initials: M
authors.lastname: Fojta
authors.forename: Jan
authors.initials: J
authors.lastname: Smarda
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D015398:Signal Transduction; D059003:Topoisomerase Inhibitors / Q000494:pharmacology*
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D003374:Coumarins; D004268:DNA-Binding Proteins; D059003:Topoisomerase Inhibitors; C051122:wedelolactone; D004250:DNA Topoisomerases, Type II