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Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

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 ca...

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Autores principales: Samec, Marek, Liskova, Alena, Koklesova, Lenka, Mersakova, Sandra, Strnadel, Jan, Kajo, Karol, Pec, Martin, Zhai, Kevin, Smejkal, Karel, Mirzaei, Sepideh, Hushmandi, Kiavash, Ashrafizadeh, Milad, Saso, Luciano, Brockmueller, Aranka, Shakibaei, Mehdi, Büsselberg, Dietrich, Kubatka, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794792/
https://www.ncbi.nlm.nih.gov/pubmed/33401572
http://dx.doi.org/10.3390/cancers13010130
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author Samec, Marek
Liskova, Alena
Koklesova, Lenka
Mersakova, Sandra
Strnadel, Jan
Kajo, Karol
Pec, Martin
Zhai, Kevin
Smejkal, Karel
Mirzaei, Sepideh
Hushmandi, Kiavash
Ashrafizadeh, Milad
Saso, Luciano
Brockmueller, Aranka
Shakibaei, Mehdi
Büsselberg, Dietrich
Kubatka, Peter
author_facet Samec, Marek
Liskova, Alena
Koklesova, Lenka
Mersakova, Sandra
Strnadel, Jan
Kajo, Karol
Pec, Martin
Zhai, Kevin
Smejkal, Karel
Mirzaei, Sepideh
Hushmandi, Kiavash
Ashrafizadeh, Milad
Saso, Luciano
Brockmueller, Aranka
Shakibaei, Mehdi
Büsselberg, Dietrich
Kubatka, Peter
author_sort Samec, Marek
collection PubMed
description 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. ABSTRACT: 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.
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spelling pubmed-77947922021-01-10 Flavonoids Targeting HIF-1: Implications on Cancer Metabolism Samec, Marek Liskova, Alena Koklesova, Lenka Mersakova, Sandra Strnadel, Jan Kajo, Karol Pec, Martin Zhai, Kevin Smejkal, Karel Mirzaei, Sepideh Hushmandi, Kiavash Ashrafizadeh, Milad Saso, Luciano Brockmueller, Aranka Shakibaei, Mehdi Büsselberg, Dietrich Kubatka, Peter Cancers (Basel) Review 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. ABSTRACT: 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. MDPI 2021-01-03 /pmc/articles/PMC7794792/ /pubmed/33401572 http://dx.doi.org/10.3390/cancers13010130 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Samec, Marek
Liskova, Alena
Koklesova, Lenka
Mersakova, Sandra
Strnadel, Jan
Kajo, Karol
Pec, Martin
Zhai, Kevin
Smejkal, Karel
Mirzaei, Sepideh
Hushmandi, Kiavash
Ashrafizadeh, Milad
Saso, Luciano
Brockmueller, Aranka
Shakibaei, Mehdi
Büsselberg, Dietrich
Kubatka, Peter
Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
title Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
title_full Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
title_fullStr Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
title_full_unstemmed Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
title_short Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
title_sort flavonoids targeting hif-1: implications on cancer metabolism
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794792/
https://www.ncbi.nlm.nih.gov/pubmed/33401572
http://dx.doi.org/10.3390/cancers13010130
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