Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

J 2021

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

SAMEC, M., A. LISKOVA, L. KOKLESOVA, S. MERSAKOVA, J. STRNADEL et. al.

Basic information

Original name

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Authors

SAMEC, M., A. LISKOVA, L. KOKLESOVA, S. MERSAKOVA, J. STRNADEL, K. KAJO, M. PEC, K. ZHAI, Karel ŠMEJKAL (203 Czech Republic, belonging to the institution), S. MIRZAEI, K. HUSHMANDI, M. ASHRAFIZADEH, L. SASO, A. BROCKMUELLER, M. SHAKIBAEI, D. BUSSELBERG and P. KUBATKA (guarantor)

Edition

Cancers, BASEL, MDPI, 2021, 2072-6694

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.575

RIV identification code

RIV/00216224:14160/21:00123950

Organization unit

Faculty of Pharmacy

DOI

http://dx.doi.org/10.3390/cancers13010130

UT WoS

000605815500001

Keywords in English

cancer; Warburg effect; HIF-1; flavonoids

Abstract

V originále

Simple Summary This comprehensive review discusses the anticancer effects of plant phenolic compounds, known as flavonoids, through the targeting of HIF-1 and critical enzymes contributing to the Warburg effect. Connections between HIF-1 and metabolic reprogramming seem to play a crucial role in cancer progression. The core of presented paper summarizes the current knowledge about the in vitro and in vivo efficacy of flavonoids against aerobic glycolysis and HIF-1 activity. Despite the lack of clinical evidence, we emphasize the possibility of introducing flavonoids (targeting HIF-1) to the clinical research considering predictive, preventive, and/or personalized medical approach. Tumor hypoxia is described as an oxygen deprivation in malignant tissue. The hypoxic condition is a consequence of an imbalance between rapidly proliferating cells and a vascularization that leads to lower oxygen levels in tumors. Hypoxia-inducible factor 1 (HIF-1) is an essential transcription factor contributing to the regulation of hypoxia-associated genes. Some of these genes modulate molecular cascades associated with the Warburg effect and its accompanying pathways and, therefore, represent promising targets for cancer treatment. Current progress in the development of therapeutic approaches brings several promising inhibitors of HIF-1. Flavonoids, widely occurring in various plants, exert a broad spectrum of beneficial effects on human health, and are potentially powerful therapeutic tools against cancer. Recent evidences identified numerous natural flavonoids and their derivatives as inhibitors of HIF-1, associated with the regulation of critical glycolytic components in cancer cells, including pyruvate kinase M2(PKM2), lactate dehydrogenase (LDHA), glucose transporters (GLUTs), hexokinase II (HKII), phosphofructokinase-1 (PFK-1), and pyruvate dehydrogenase kinase (PDK). Here, we discuss the results of most recent studies evaluating the impact of flavonoids on HIF-1 accompanied by the regulation of critical enzymes contributing to the Warburg phenotype. Besides, flavonoid effects on glucose metabolism via regulation of HIF-1 activity represent a promising avenue in cancer-related research. At the same time, only more-in depth investigations can further elucidate the mechanistic and clinical connections between HIF-1 and cancer metabolism.

Citovat

SAMEC, M., A. LISKOVA, L. KOKLESOVA, S. MERSAKOVA, J. STRNADEL, K. KAJO, M. PEC, K. ZHAI, Karel ŠMEJKAL, S. MIRZAEI, K. HUSHMANDI, M. ASHRAFIZADEH, L. SASO, A. BROCKMUELLER, M. SHAKIBAEI, D. BUSSELBERG and P. KUBATKA. Flavonoids Targeting HIF-1: Implications on Cancer Metabolism. Cancers. BASEL: MDPI, 2021, vol. 13, No 1, p. 1-27. ISSN 2072-6694. Available from: https://dx.doi.org/10.3390/cancers13010130.

@article{1826758,
   author = {Samec, M. and Liskova, A. and Koklesova, L. and Mersakova, S. and Strnadel, J. and Kajo, K. and Pec, M. and Zhai, K. and Šmejkal, Karel and Mirzaei, S. and Hushmandi, K. and Ashrafizadeh, M. and Saso, L. and Brockmueller, A. and Shakibaei, M. and Busselberg, D. and Kubatka, P.},
   article_location = {BASEL},
   article_number = {1},
   doi = {http://dx.doi.org/10.3390/cancers13010130},
   keywords = {cancer; Warburg effect; HIF-1; flavonoids},
   language = {eng},
   issn = {2072-6694},
   journal = {Cancers},
   title = {Flavonoids Targeting HIF-1: Implications on Cancer Metabolism},
   url = {https://www.mdpi.com/2072-6694/13/1/130},
   volume = {13},
   year = {2021}
}

TY  - JOUR
ID  - 1826758
AU  - Samec, M. - Liskova, A. - Koklesova, L. - Mersakova, S. - Strnadel, J. - Kajo, K. - Pec, M. - Zhai, K. - Šmejkal, Karel - Mirzaei, S. - Hushmandi, K. - Ashrafizadeh, M. - Saso, L. - Brockmueller, A. - Shakibaei, M. - Busselberg, D. - Kubatka, P.
PY  - 2021
TI  - Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
JF  - Cancers
VL  - 13
IS  - 1
SP  - 1-27
EP  - 1-27
PB  - MDPI
SN  - 20726694
KW  - cancer
KW  - Warburg effect
KW  - HIF-1
KW  - flavonoids
UR  - https://www.mdpi.com/2072-6694/13/1/130
N2  - Simple Summary This comprehensive review discusses the anticancer effects of plant phenolic compounds, known as flavonoids, through the targeting of HIF-1 and critical enzymes contributing to the Warburg effect. Connections between HIF-1 and metabolic reprogramming seem to play a crucial role in cancer progression. The core of presented paper summarizes the current knowledge about the in vitro and in vivo efficacy of flavonoids against aerobic glycolysis and HIF-1 activity. Despite the lack of clinical evidence, we emphasize the possibility of introducing flavonoids (targeting HIF-1) to the clinical research considering predictive, preventive, and/or personalized medical approach. Tumor hypoxia is described as an oxygen deprivation in malignant tissue. The hypoxic condition is a consequence of an imbalance between rapidly proliferating cells and a vascularization that leads to lower oxygen levels in tumors. Hypoxia-inducible factor 1 (HIF-1) is an essential transcription factor contributing to the regulation of hypoxia-associated genes. Some of these genes modulate molecular cascades associated with the Warburg effect and its accompanying pathways and, therefore, represent promising targets for cancer treatment. Current progress in the development of therapeutic approaches brings several promising inhibitors of HIF-1. Flavonoids, widely occurring in various plants, exert a broad spectrum of beneficial effects on human health, and are potentially powerful therapeutic tools against cancer. Recent evidences identified numerous natural flavonoids and their derivatives as inhibitors of HIF-1, associated with the regulation of critical glycolytic components in cancer cells, including pyruvate kinase M2(PKM2), lactate dehydrogenase (LDHA), glucose transporters (GLUTs), hexokinase II (HKII), phosphofructokinase-1 (PFK-1), and pyruvate dehydrogenase kinase (PDK). Here, we discuss the results of most recent studies evaluating the impact of flavonoids on HIF-1 accompanied by the regulation of critical enzymes contributing to the Warburg phenotype. Besides, flavonoid effects on glucose metabolism via regulation of HIF-1 activity represent a promising avenue in cancer-related research. At the same time, only more-in depth investigations can further elucidate the mechanistic and clinical connections between HIF-1 and cancer metabolism.
ER  -

SAMEC, M., A. LISKOVA, L. KOKLESOVA, S. MERSAKOVA, J. STRNADEL, K. KAJO, M. PEC, K. ZHAI, Karel ŠMEJKAL, S. MIRZAEI, K. HUSHMANDI, M. ASHRAFIZADEH, L. SASO, A. BROCKMUELLER, M. SHAKIBAEI, D. BUSSELBERG and P. KUBATKA. Flavonoids Targeting HIF-1: Implications on Cancer Metabolism. \textit{Cancers}. BASEL: MDPI, 2021, vol.~13, No~1, p.~1-27. ISSN~2072-6694. Available from: https://dx.doi.org/10.3390/cancers13010130.

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