Flavonoids targeting HIF-1: implications on cancer metabolism

Samec, Marek and Liskova, Alena and Koklesova, Lenka and Mersakova, Sandra and Strnadel, Jan and Kajo, Karol and Pec, Martin and Zhai, Kevin and Smejkal, Karel and Mirzaei, Sepideh and Hushmandi, Kiavash and Ashrafizadeh, Milad and Saso, Luciano and Brockmueller, Aranka and Shakibaei, Mehdi and Büsselberg, Dietrich and Kubatka, Peter (2021) Flavonoids targeting HIF-1: implications on cancer metabolism. Cancers, 13 (1). ISSN 2072-6694

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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.
Item Type: Article
Uncontrolled Keywords: Cancer; Flavonoids; HIF-1; Warburg effect
Divisions: Faculty of Engineering and Natural Sciences
Sabancı University Nanotechnology Research and Application Center
Depositing User: Milad Ashrafizadeh
Date Deposited: 03 Sep 2022 13:12
Last Modified: 03 Sep 2022 13:12
URI: https://research.sabanciuniv.edu/id/eprint/43396

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