Flavonoids against the Warburg phenotype-concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism

被引：102

作者：

Samec, Marek ^{[1
]}

Liskova, Alena ^{[1
]}

Koklesova, Lenka ^{[1
]}

Samuel, Samson Mathews ^{[2
]}

Zhai, Kevin ^{[2
]}

Buhrmann, Constanze ^{[3
]}

Varghese, Elizabeth ^{[2
]}

Abotaleb, Mariam ^{[2
]}

Qaradakhi, Tawar ^{[4
]}

Zulli, Anthony ^{[4
]}

Kello, Martin ^{[5
]}

Mojzis, Jan ^{[5
]}

Zubor, Pavol ^{[6
,7
]}

Kwon, Taeg Kyu ^{[8
,9
]}

Shakibaei, Mehdi ^{[3
]}

Busselberg, Dietrich ^{[2
]}

Sarria, Gustavo R. ^{[10
]}

Golubnitschaja, Olga ^{[11
]}

Kubatka, Peter ^{[12
]}

机构：

[1] Comenius Univ, Jessenius Fac Med, Clin Obstet & Gynecol, Martin 03601, Slovakia

[2] Qatar Fdn, Dept Physiol & Biophys, Educ City, Weill Cornell Med Qatar, Doha 24144, Qatar

[3] Ludwig Maximilian Univ Munich, Fac Med, Inst Anat, Chair Vegetat Anat,Musculoskeletal Res Grp & Tumo, D-80336 Munich, Germany

[4] Victoria Univ, Inst Hlth & Sport, Melbourne, Vic 3011, Australia

[5] Safarik Univ, Fac Med, Dept Pharmacol, Kosice 04011, Slovakia

[6] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Gynecol Oncol, N-0379 Oslo, Norway

[7] OBGY Hlth & Care Ltd, Zilina 01001, Slovakia

[8] Keimyung Univ, Dept Immunol, Daegu 42601, South Korea

[9] Keimyung Univ, Sch Med, Daegu 42601, South Korea

[10] Rheinische Friedrich Wilhelms Univ Bonn, Univ Hosp Bonn, Dept Radiat Oncol, Bonn, Germany

[11] Rheinische Friedrich Wilhelms Univ Bonn, Univ Hosp Bonn, Dept Radiat Oncol, Predict Prevent Personalised 3P Med, Bonn, Germany

[12] Comenius Univ, Jessenius Fac Med, Dept Med Biol, Martin 03601, Slovakia

来源：

EPMA JOURNAL | 2020年 / 11卷 / 03期

关键词：

Predictive preventive personalised medicine (PPPM; 3PM); Cancer; Warburg phenotype; Flavonoids; Anticancer effect; Cell metabolism; Co-morbidities; Malignancy; Disease manifestation; Age; Patient stratification; Aggressive metastatic disease; Multi-omics; Biomarker patterns; Liquid biopsy; Modifiable risk factors; Risk assessment; Microcirculation; Systemic hypoxia; Ischemic lesions; Prognosis; Individualised patient profiles; Treatment algorithms; Liver malignancy; Triple-negative breast cancer; Prostate cancer; Pregnancy; Chemoresistance; Radioresistance; Glucose metabolism; Oxidative phosphorylation; Proliferation; Metabolic reprogramming; Positron emission tomography; Magnetic resonance spectroscopy; Tumour imaging; FDG-PET; Glucose intake; PET-CT; Individual outcome; Palliative medicine; Polyphenols; Glycolysis; Carcinogenesis; Prognostic markers; Aerobic glycolysis; Glycolytic inhibitors; Pleiotropic activity; HIF-1; BREAST-CANCER; PROSTATE-CANCER; GLUCOSE-UPTAKE; AEROBIC GLYCOLYSIS; FLAMMER SYNDROME; HEXOKINASE II; IN-VITRO; INHIBITS GLYCOLYSIS; HODGKIN LYMPHOMA; CARCINOMA-CELLS;

D O I：

10.1007/s13167-020-00217-y

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The Warburg effect is characterised by increased glucose uptake and lactate secretion in cancer cells resulting from metabolic transformation in tumour tissue. The corresponding molecular pathways switch from oxidative phosphorylation to aerobic glycolysis, due to changes in glucose degradation mechanisms known as the 'Warburg reprogramming' of cancer cells. Key glycolytic enzymes, glucose transporters and transcription factors involved in the Warburg transformation are frequently dysregulated during carcinogenesis considered as promising diagnostic and prognostic markers as well as treatment targets. Flavonoids are molecules with pleiotropic activities. The metabolism-regulating anticancer effects of flavonoids are broadly demonstrated in preclinical studies. Flavonoids modulate key pathways involved in the Warburg phenotype including but not limited to PKM2, HK2, GLUT1 and HIF-1. The corresponding molecular mechanisms and clinical relevance of 'anti-Warburg' effects of flavonoids are discussed in this review article. The most prominent examples are provided for the potential application of targeted 'anti-Warburg' measures in cancer management. Individualised profiling and patient stratification are presented as powerful tools for implementing targeted 'anti-Warburg' measures in the context of predictive, preventive and personalised medicine.

引用

页码：377 / 398

页数：22

共 234 条

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