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Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

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submitted on 2024-06-26, 05:00 and posted on 2024-06-26, 05:00 authored by Marek Samec, Alena Liskova, Lenka Koklesova, Sandra Mersakova, Jan Strnadel, Karol Kajo, Martin Pec, Kevin Zhai, Karel Smejkal, Sepideh Mirzaei, Kiavash Hushmandi, Milad Ashrafizadeh, Luciano Saso, Aranka Brockmueller, Mehdi Shakibaei, Dietrich Büsselberg, Peter Kubatka

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.

Other Information

Published in: Cancers
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3390/cancers13010130

Funding

Ministry of Education of the Slovak Republic (VEGA 1/0136/19).

Qatar National Research Fund (NPRP11S-1214-170101), Anti-diabetic drugs in the treatment of breast cancer - identifying the molecular mechanism(s) and key biomarker(s).

History

Language

  • English

Publisher

MDPI

Publication Year

  • 2021

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Weill Cornell Medicine - Qatar

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    Weill Cornell Medicine - Qatar

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