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Akt plays an important role in progression and chemoresistance of human cancer. 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. 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.I hereby declare that the University of Ulm shall have the rights to store my dissertation and associated materials on digital storage systems, to publish them in public networks and to forward them to the German National Library for storage and public access.
I hereby declare that the University of Ulm shall have the rights to store my dissertation and associated materials on digital storage systems, to publish them in public networks and to forward them to the German National Library for storage and public access. Akt is a family of kinases controling cell metabolism, proliferation and apoptosis.
Akt plays an important role in progression and chemoresistance of human cancer. Context: In order for balance to be maintained, the postural control system must process above all visual, vestibular and proprioceptive information and translate this input into appropriate motor responses.
Brain voltage-gated sodium channels are complexes of a pore-forming alpha subunit and auxiliary beta1 and beta2 subunits with modulation effects. The Lost Secret of Dissertation. 49 (0) helpdeskuni-ulm.
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