TY - JOUR
T1 - A novel substrate mimetic inhibitor of PKB/Akt inhibits prostate cancer tumor growth in mice by blocking the PKB pathway
AU - Litman, Pninit
AU - Ohne, Osnat
AU - Ben-Yaakov, Shirly
AU - Shemesh-Darvish, Liron
AU - Yechezkel, Tamar
AU - Salitra, Yosef
AU - Rubnov, Shai
AU - Cohen, Ilana
AU - Senderowitz, Hanoch
AU - Kidron, Dvora
AU - Livnah, Oded
AU - Levitzki, Alexander
AU - Livnah, Nurit
PY - 2007/4/24
Y1 - 2007/4/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34247484461&partnerID=8YFLogxK
U2 - 10.1021/bi061928s
DO - 10.1021/bi061928s
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C2 - 17397140
AN - SCOPUS:34247484461
SN - 0006-2960
VL - 46
SP - 4716
EP - 4724
JO - Biochemistry
JF - Biochemistry
IS - 16
ER -