Abstract：
:We describe a novel, potent peptide substrate mimetic inhibitor of protein kinase B (PKB/Akt). The compound selectively kills prostate cancer cells, in which PKB is highly activated, but not normal cells, or cancer cells in which PKB is not activated. The inhibitor induces apoptosis and inhibits the phosphorylation of PKB substrates in prostate cancer cell lines and significantly increases the efficacy of chemotherapy agents to induce prostate cancer cell death, when given in combination. In vivo, the inhibitor exhibits a strong antitumor effect in two prostate cancer mouse models. Moreover, treated animals develop significantly less lung metastases compared to untreated ones, and the effect is accompanied by a significant decrease in blood PSA [prostate-specific antigen] levels in treated animals. This compound and its potential analogues may be developed into novel, potent, and safe anticancer agents, both as stand-alone treatment and in combination with other chemotherapy agents.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Litman P,Ohne O,Ben-Yaakov S,Shemesh-Darvish L,Yechezkel T,Salitra Y,Rubnov S,Cohen I,Senderowitz H,Kidron D,Livnah O,Levitzki A,Livnah Ndoi
10.1021/bi061928ssubject
Has Abstractpub_date
2007-04-24 00:00:00pages
4716-24issue
16eissn
0006-2960issn
1520-4995journal_volume
46pub_type
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