Aldo-Keto Reductase AKR1C1-AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy

被引：98

作者：

Zeng, Chen-Ming ^{[1
]}

Chang, Lin-Lin ^{[1
]}

Ying, Mei-Dan ^{[1
]}

Cao, Ji ^{[1
]}

He, Qiao-Jun ^{[1
]}

Zhu, Hong ^{[1
]}

Yang, Bo ^{[1
]}

机构：

[1] Zhejiang Univ, Coll Pharmaceut Sci, Inst Pharmacol & Toxicol, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou, Zhejiang, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

aldo-keto reductases; catalytic-dependent; catalytic-independent; inhibitor; therapy; RESISTANT PROSTATE-CANCER; 5 17-BETA-HYDROXYSTEROID-DEHYDROGENASE AKR1C3; 20-ALPHA-HYDROXYSTEROID DEHYDROGENASE AKR1C1; STEROIDOGENIC ENZYME AKR1C3; PROSTAGLANDIN-F SYNTHASE; UBIQUITIN LIGASE SIAH2; HUMAN BREAST-CANCER; MODEL CELL-LINES; 1 MEMBER C3; SELECTIVE INHIBITORS;

D O I：

10.3389/fphar.2017.00119

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aldo-keto reductases comprise of AKR1C1-AKR1C4, four enzymes that catalyze NADPH dependent reductions and have been implicated in biosynthesis, intermediary metabolism, and detoxification. Recent studies have provided evidences of strong correlation between the expression levels of these family members and the malignant transformation as well as the resistance to cancer therapy. Mechanistically, most studies focus on the catalytic-dependent function of AKR1C isoforms, like their impeccable roles in prostate cancer, breast cancer, and drug resistance due to the broad substrates specificity. However, accumulating clues showed that catalytic-independent functions also played critical roles in regulating biological events. This review summarizes the catalytic-dependent and -independent roles of AKR1Cs, as well as the small molecule inhibitors targeting these family members.

引用

页数：9

共 90 条

[1] Discovery of substituted 3-(phenylamino)benzoic acids as potent and selective inhibitors of type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) [J].