Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-8-10
pubmed:abstractText
Acetyl-boswellic acids (acetyl-BA) are pentacyclic triterpenes derived from the gum resin of frankincense. We have previously shown that these compounds are effective cytotoxic agents, acting through a mechanism that appears to involve the inhibition of topoisomerase activity. We have now investigated the mechanism of action of acetyl-BA and show that these compounds are more potent inhibitors of human topoisomerases I and IIalpha than camptothecin, and amsacrine or etoposide, respectively. Our data demonstrate that acetyl-BA and, to a lesser extent, some other pentacyclic triterpenes, such as betulinic acid, ursolic acid, and oleanolic acid, inhibit topoisomerases I and IIalpha through a mechanism that does not involve stabilization of the cleavable complex or the intercalation of DNA. Surface plasmon resonance analysis revealed that topoisomerases I and IIalpha bind directly to an immobilized derivative of acetyl-BA. This acetyl-BA derivative interacts with human topoisomerases through high-affinity binding sites yielding K(D) values of 70.6 nM for topoisomerase I and 7.6 nM for topoisomerase IIalpha. Based on our data, we propose that acetyl-BA inhibit topoisomerases I and IIalpha through competition with DNA for binding to the enzyme. Thus, acetyl-BA are a unique class of dual catalytic inhibitors of human topoisomerases I and IIalpha.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type I, http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type II, http://linkedlifedata.com/resource/pubmed/chemical/DNA topoisomerase II alpha, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Lipoxygenase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase I Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase II Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Triterpenes, http://linkedlifedata.com/resource/pubmed/chemical/acetyl-11-ketoboswellic acid
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
71-81
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and IIalpha.
pubmed:affiliation
Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Germany.
pubmed:publicationType
Journal Article