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Phytochemicals as Regulators of Tumor Glycolysis and Hypoxia Signaling Pathways: Evidence from In Vitro Studies

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MEDFUTURE Research Center for Advanced Medicine, Department of Proteomics and Metabolomics, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Street 4-6, 400349 Cluj-Napoca, Romania
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Department of Pharmaceutical Biochemistry and Clinical Laboratory, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, Louis Pasteur Street 6, 400349 Cluj-Napoca, Romania
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MEDFUTURE Research Center for Advanced Medicine, Department of Translational Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Street 4-6, 400349 Cluj-Napoca, Romania
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MEDFUTURE Research Center for Advanced Medicine, Department of In Vivo Studies-Animal Facility, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Street 4-6, 400349 Cluj-Napoca, Romania
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Department of Pharmaceutical Analysis, Faculty of Pharmacy, “Iuliu Hațieganu” University of Medicine and Pharmacy, Louis Pasteur Street 6, 400349 Cluj-Napoca, Romania
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Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Paulo Santos and Lillian Barros
Pharmaceuticals 2022, 15(7), 808; https://doi.org/10.3390/ph15070808
Received: 26 May 2022 / Revised: 23 June 2022 / Accepted: 27 June 2022 / Published: 28 June 2022
(This article belongs to the Special Issue Anticancer Compounds in Medicinal Plants 2022)
The full understanding of the complex nature of cancer still faces many challenges, as cancers arise not as a result of a single target disruption but rather involving successive genetic and epigenetic alterations leading to multiple altered metabolic pathways. In this light, the need for a multitargeted, safe and effective therapy becomes essential. Substantial experimental evidence upholds the potential of plant-derived compounds to interfere in several important pathways, such as tumor glycolysis and the upstream regulating mechanisms of hypoxia. Herein, we present a comprehensive overview of the natural compounds which demonstrated, in vitro studies, an effective anticancer activity by affecting key regulators of the glycolytic pathway such as glucose transporters, hexokinases, phosphofructokinase, pyruvate kinase or lactate dehydrogenase. Moreover, we assessed how phytochemicals could interfere in HIF-1 synthesis, stabilization, accumulation, and transactivation, emphasizing PI3K/Akt/mTOR and MAPK/ERK pathways as important signaling cascades in HIF-1 activation. Special consideration was given to cell culture-based metabolomics as one of the most sensitive, accurate, and comprising approaches for understanding the response of cancer cell metabolome to phytochemicals. View Full-Text
Keywords: phytochemicals; tumor glycolysis; tumor hypoxia; Warburg effect; HIF-1 signaling pathway; metabolomics phytochemicals; tumor glycolysis; tumor hypoxia; Warburg effect; HIF-1 signaling pathway; metabolomics
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MDPI and ACS Style

Pralea, I.-E.; Petrache, A.-M.; Tigu, A.B.; Gulei, D.; Moldovan, R.-C.; Ilieș, M.; Nicoară, R.; Hegheș, S.-C.; Uifălean, A.; Iuga, C.-A. Phytochemicals as Regulators of Tumor Glycolysis and Hypoxia Signaling Pathways: Evidence from In Vitro Studies. Pharmaceuticals 2022, 15, 808. https://doi.org/10.3390/ph15070808

AMA Style

Pralea I-E, Petrache A-M, Tigu AB, Gulei D, Moldovan R-C, Ilieș M, Nicoară R, Hegheș S-C, Uifălean A, Iuga C-A. Phytochemicals as Regulators of Tumor Glycolysis and Hypoxia Signaling Pathways: Evidence from In Vitro Studies. Pharmaceuticals. 2022; 15(7):808. https://doi.org/10.3390/ph15070808

Chicago/Turabian Style

Pralea, Ioana-Ecaterina, Alina-Maria Petrache, Adrian Bogdan Tigu, Diana Gulei, Radu-Cristian Moldovan, Maria Ilieș, Raul Nicoară, Simona-Codruța Hegheș, Alina Uifălean, and Cristina-Adela Iuga. 2022. "Phytochemicals as Regulators of Tumor Glycolysis and Hypoxia Signaling Pathways: Evidence from In Vitro Studies" Pharmaceuticals 15, no. 7: 808. https://doi.org/10.3390/ph15070808

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