J 2021

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

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

Základní údaje

Originální název

Flavonoids Targeting HIF-1: Implications on Cancer Metabolism

Autoři

SAMEC, M., A. LISKOVA, L. KOKLESOVA, S. MERSAKOVA, J. STRNADEL, K. KAJO, M. PEC, K. ZHAI, Karel ŠMEJKAL (203 Česká republika, domácí), S. MIRZAEI, K. HUSHMANDI, M. ASHRAFIZADEH, L. SASO, A. BROCKMUELLER, M. SHAKIBAEI, D. BUSSELBERG a P. KUBATKA (garant)

Vydání

Cancers, BASEL, MDPI, 2021, 2072-6694

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 6.575

Kód RIV

RIV/00216224:14160/21:00123950

Organizační jednotka

Farmaceutická fakulta

UT WoS

000605815500001

Klíčová slova anglicky

cancer; Warburg effect; HIF-1; flavonoids

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 15. 3. 2022 14:24, JUDr. Sabina Krejčiříková

Anotace

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.