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Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
M. Samec, A. Liskova, L. Koklesova, S. Mersakova, J. Strnadel, K. Kajo, M. Pec, K. Zhai, K. Smejkal, S. Mirzaei, K. Hushmandi, M. Ashrafizadeh, L. Saso, A. Brockmueller, M. Shakibaei, D. Büsselberg, P. Kubatka
Language English Country Switzerland
Document type Journal Article, Review
Grant support
VEGA 1/0136/19
Scientific Grant Agency of the Ministry of Education of the Slovak Republic
NPRP 11S-1214-170101
National Priorities Research Program grant (awarded to Professor Dr. Dietrich Büsselberg, June 2019-Current) from the Qatar National Research Fund
NLK
Free Medical Journals
from 2009
PubMed Central
from 2009
Europe PubMed Central
from 2009
ProQuest Central
from 2009-01-01
Open Access Digital Library
from 2009-01-01
Open Access Digital Library
from 2009-01-01
ROAD: Directory of Open Access Scholarly Resources
from 2009
- Publication type
- Journal Article MeSH
- Review MeSH
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.
Department of Pathology St Elizabeth Cancer Institute Hospital 81250 Bratislava Slovakia
Sabanci University Nanotechnology Research and Application Center Tuzla 34956 Istanbul Turkey
References provided by Crossref.org
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