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AuthorEstrada, Aidee Constanzadc.contributor.author
Date of accession2016-03-14T15:23:04Zdc.date.accessioned
Available in OPARU since2016-03-14T15:23:04Zdc.date.available
Year of creation2007dc.date.created
AbstractAkt is a family of kinases controling cell metabolism, proliferation and apoptosis. Akt plays an important role in progression and chemoresistance of human cancer. We analyzed function of Akt in androgen-dependent LNCaP and androgen-independent PC-3 and DU 145 prostate cancer cells. Akt1 and Akt2, but not the Akt3 isoform are expressed and constitutively active in all cell lines. Three structurally different Akt inhibitors exerted cytotoxic effect on prostate cancer cells indicating that the Akt pathway is indispensable for cancer cell proliferation. The oleogum resins from Boswellia species contain a complex mixture of triterpenoids that possess biological activities including antitumor properties. In search for well-tolerated and stable Akt inhibitors, we have isolated several tetracyclic triterpenoids from the oleogum resin of Boswellia carterii and purified them to chemical homogeneity. Triterpenoids potently inhibited the activities of human recombinant Akt1 and Akt2 in in vitro kinase assays. Similarly, the triterpenoids inhibited Akt activity immunoprecipitated from PC-3 cells, but did not affect the activity of immunoprecipitated IKK. The triterpenoids also inhibited the phosphorylation of cellular Akt, b-catenin and glycogen synthase kinase (GSK)-3b, whereas extracellular signal-regulated kinase (ERK)1/2 phosphorylation remained unaffected. In addition, the compounds down-regulated the expression of the crucial cell cycle regulators cyclin D1 and c-myc followed by reduction of phosphorylation of retinoblastoma protein, cell cycle arrest and apoptosis. Thus, the inhibition of Akt activity is sufficient to trigger apoptosis in prostate cancer cells. Tetracyclic triterpenoids inhibiting Akt in chemoresistant human prostate cancer.dc.description.abstract
Languageendc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (Fassung vom 01.10.2008)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v2dc.rights.uri
KeywordAktdc.subject
KeywordCell cycle arrestdc.subject
KeywordTetracyclic triterpenoidsdc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHApoptosisdc.subject.mesh
MeSHProstatic neoplasmsdc.subject.mesh
TitleInhibition Akt by tetracyclic triterpenoids induces cell cycle arrest and apoptosis in prostate cancer cells.dc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-1585dc.identifier.doi
PPN598244441dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-67706dc.identifier.urn
FacultyMedizinische Fakultätuulm.affiliationGeneral
Date of activation2009-04-20T09:24:29Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionZ: J-H 13.237; W: W-H 11.681uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS ID6770uulm.vtsID
CategoryPublikationenuulm.category
Bibliographyuulmuulm.bibliographie


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