The efficacy and selectivity of tumor cell killing by Akt inhibitors are substantially increased by chloroquine

被引：61

作者：

Hu, Changkun ^{[1
]}

Solomon, V. Raja ^{[1
]}

Ulibarri, Gerardo ^{[2
]}

Lee, Hoyun ^{[1
]}

机构：

[1] Sudbury Reg Hosp, Northeastern Ontario Reg Canc Ctr, Tumor Biol Grp, Sudbury, ON P3E 5J1, Canada

[2] Laurentian Univ, Dept Chem & Biochem, Sudbury, ON P3E 2C6, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 17期

关键词：

chloroquine; PI3K-Akt inhibitors; breast cancer; cell killing; sensitization; chemotherapeutics;

D O I：

10.1016/j.bmc.2008.07.076

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

This study was to evaluate the enhancement value of chloroquine (CQ) in cancer cell killing when used in combination with Akt inhibitors. The results showed that the combination of CQ and Akt inhibitors is much more effective than either one alone. Importantly, the CQ-mediated chemosensitization of cell killing effects by Akt inhibitors is cancer specific. In particular, when combined with 10 mu M CQ, 1,3-dihydro-1-(1-((4-(6-phenyl-1H-imidazo[4,5-g]quinoxalin-7-yl)phenyl)methyl)-4-piperidinyl)-2H-benzimidazol-2-one (an Akt1 and 2 inhibitor; compound 8) killed cancer cells 10-120 times more effectively than normal cells. Thus, CQ is a very effective and cancer-specific chemosensitizer when used in combination with Akt inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：7888 / 7893

页数：6

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