The multifaceted contribution of a-ketoglutarate to tumor progression: An opportunity to exploit?

被引：69

作者：

Abla, Houda ^{[1
]}

Sollazzo, Manuela ^{[1
]}

Gasparre, Giuseppe ^{[2
,3
]}

Iommarini, Luisa ^{[1
]}

Porcelli, Anna Maria ^{[1
,4
]}

机构：

[1] Univ Bologna, Dept Pharm & Biotechnol FaBit, Via Selmi 3, I-40126 Bologna, Italy

[2] Univ Bologna, Dept Med & Surg Sci DIMEC, Unit Med Genet, Via Massarenti 9, I-40138 Bologna, Italy

[3] Univ Bologna, Ctr Appl Biomed Res CRBA, Via Massarenti 9, I-40138 Bologna, Italy

[4] Univ Bologna, Interdept Ctr Ind Res CIRI Life Sci & Hlth Techno, Via Tolara Sopra 41-E, I-40064 Ozzano Dellemilia, Italy

来源：

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY | 2020年 / 98卷

基金：

欧盟地平线“2020”;

关键词：

alpha-Ketoglutarate; Tumor progression; Hypoxia; Epigenetics; Cancer metabolism; Drosophila melanogaster; ORNITHINE ALPHA-KETOGLUTARATE; CITRIC-ACID CYCLE; ISOCITRATE DEHYDROGENASE; IDH2; MUTATIONS; ONCOMETABOLITE; 2-HYDROXYGLUTARATE; DROSOPHILA-MELANOGASTER; REDUCTIVE CARBOXYLATION; GLUTAMINE-METABOLISM; PROLYL-HYDROXYLASE; HYDROGEN-PEROXIDE;

D O I：

10.1016/j.semcdb.2019.05.031

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The thriving field that constitutes cancer metabolism has unveiled some groundbreaking facts over the past two decades, at the heart of which is the TCA cycle and its intermediates. As such and besides its metabolic role, alpha-ketoglutarate was shown to withstand a wide range of physiological reactions from protection against oxidative stress, collagen and bone maintenance to development and immunity. Most importantly, it constitutes the rate-limiting substrate of 2-oxoglutarate-dependent dioxygenases family enzymes, which are involved in hypoxia sensing and in the shaping of cellular epigenetic landscape, two major drivers of oncogenic transformation. Based on literature reports, we hereby review the benefits of this metabolite as a possible novel adjuvant therapeutic opportunity to target tumor progression. This article is part of the special issue "Mitochondrial metabolic alterations in cancer cells and related therapeutic targets".

引用

页码：26 / 33

页数：8

共 109 条

[1] Citric Acid Cycle and Role of its Intermediates in Metabolism [J].

Akram, Muhammad .

CELL BIOCHEMISTRY AND BIOPHYSICS, 2014, 68 (03) :475-478

[2] Analysis of the hypoxia-sensing pathway in Drosophila melanogaster [J].

Arquier, N ;

Vigne, P ;

Duplan, E ;

Hsu, T ;

Therond, PP ;

Frelin, C ;

D'Angelo, G .

BIOCHEMICAL JOURNAL, 2006, 393 :471-480

[3] Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma [J].

Astuti, D ;

Latif, F ;

Dallol, A ;

Dahia, PLM ;

Douglas, F ;

George, E ;

Sköldberg, F ;

Husebye, ES ;

Eng, C ;

Maher, ER .

AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 69 (01) :49-54

[4] α-ketoglutarate dehydrogenase inhibition counteracts breast cancer-associated lung metastasis [J].

Atlante, Sandra ;

Visintin, Alessia ;

Marini, Elisabetta ;

Savoia, Matteo ;

Dianzani, Chiara ;

Giorgis, Marta ;

Surun, Duran ;

Maione, Federica ;

Schnutgen, Frank ;

Farsetti, Antonella ;

Zeiher, Andreas M. ;

Bertinaria, Massimo ;

Giraudo, Enrico ;

Spallotta, Francesco ;

Cencioni, Chiara ;

Gaetano, Carlo .

CELL DEATH & DISEASE, 2018, 9

[5] Protective effects of alpha-ketoglutarate against aluminum toxicity in Drosophila melanogaster [J].

Bayliak, Maria M. ;

Lylyk, Maria P. ;

Gospodaryov, Dmytro V. ;

Kotsyubynsky, Volodymyr O. ;

Butenko, Nataliia V. ;

Storey, Kenneth B. ;

Lushchak, Volodymyr I. .

COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, 2019, 217 :41-53

[6] Alpha-ketoglutarate reduces ethanol toxicity in Drosophila melanogaster by enhancing alcohol dehydrogenase activity and antioxidant capacity [J].

Bayliak, Maria M. ;

Shmihel, Halyna V. ;

Lylyk, Maria P. ;

Storey, Kenneth B. ;

Lushchak, Volodymyr I. .

ALCOHOL, 2016, 55 :23-33

[7] Alpha-ketoglutarate attenuates toxic effects of sodium nitroprusside and hydrogen peroxide in Drosophila melanogaster [J].

Bayliak, Maria M. ;

Shmihel, Halyna V. ;

Lylyk, Maria P. ;

Vytvytska, Oksana M. ;

Storey, Janet M. ;

Storey, Kenneth B. ;

Lushchak, Volodymyr I. .

ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, 2015, 40 (02) :650-659

[8] Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma [J].

Baysal, BE ;

Ferrell, RE ;

Willett-Brozick, JE ;

Lawrence, EC ;

Myssiorek, D ;

Bosch, A ;

van der Mey, A ;

Taschner, PEM ;

Rubinstein, WS ;

Myers, EN ;

Richard, CW ;

Cornelisse, CJ ;

Devilee, P ;

Devlin, B .

SCIENCE, 2000, 287 (5454) :848-851

[9] Acute toxicity of some synthetic cyanogens in rats and their response to oral treatment with alpha-ketoglutarate [J].

Bhattacharya, R. ;

Satpute, R. M. ;

Hariharakrishnan, J. ;

Tripathi, H. ;

Saxena, P. B. .

FOOD AND CHEMICAL TOXICOLOGY, 2009, 47 (09) :2314-2320

[10] α-Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway [J].

Cai, Xingcai ;

Yuan, Yexian ;

Liao, Zhengrui ;

Xing, Kongping ;

Zhu, Canjun ;

Xu, Yaqiong ;

Yu, Lulu ;

Wang, Lina ;

Wang, Songbo ;

Zhu, Xiaotong ;

Gao, Ping ;

Zhang, Yongliang ;

Jiang, Qingyan ;

Xu, Pingwen ;

Shu, Gang .

FASEB JOURNAL, 2018, 32 (01) :488-499

← 1 2 3 4 5 6 7 8 9 10 →