Significance of flavonoids targeting PI3K/Akt/HIF-1a signaling
pathway in therapy-resistant cancer cells - A potential
contribution to the predictive, preventive, and personalized
medicine

J 2024

Significance of flavonoids targeting PI3K/Akt/HIF-1a signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine

MAZURAKOVA, Alena; Lenka KOKLESOVA; Sandra Hurta CSIZMAR; Marek SAMEC; Aranka BROCKMUELLER et. al.

Základní údaje

Originální název

Significance of flavonoids targeting PI3K/Akt/HIF-1a signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine

Autoři

Vydání

Journal of Advanced Research, Amsterdam, Elsevier, 2024, 2090-1232

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 13.000

Kód RIV

RIV/00216224:14160/24:00139008

Organizační jednotka

Farmaceutická fakulta

DOI

https://doi.org/10.1016/j.jare.2023.02.015

UT WoS

001150282600001

EID Scopus

2-s2.0-85149785938

Klíčová slova anglicky

Cancer; Resistance; Glycolysis; Flavonoids; predictive preventive personalized; medicine (PPPM / 3PM); Primary secondary tertiary care; Health-to-disease transition; WHO

Štítky

rivok, ÚPL

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 30. 7. 2025 14:20, Mgr. Michal Petr

Anotace

V originále

Background: Cancer management faces multiple obstacles, including resistance to current therapeutic approaches. In the face of challenging microenvironments, cancer cells adapt metabolically to maintain their supply of energy and precursor molecules for biosynthesis and thus sustain rapid proliferation and tumor growth. Among the various metabolic adaptations observed in cancer cells, the altered glucose metabolism is the most widely studied. The aberrant glycolytic modification in cancer cells has been associated with rapid cell division, tumor growth, cancer progression, and drug resistance. The higher rates of glycolysis in cancer cells, as a hallmark of cancer progression, is modulated by the transcription factor hypoxia inducible factor 1 alpha (HIF-1a), a downstream target of the PI3K/Akt signaling, the most deregulated pathway in cancer.Aim of Review: We provide a detailed overview of current, primarily experimental, evidence on the potential effectiveness of flavonoids to combat aberrant glycolysis-induced resistance of cancer cells to conventional and targeted therapies. The manuscript focuses primarily on flavonoids reducing cancer resistance via affecting PI3K/Akt, HIF-1a (as the transcription factor critical for glucose metabolism of cancer cells that is regulated by PI3K/Akt pathway), and key glycolytic mediators downstream of PI3K/Akt/HIF-1a signaling (glucose transporters and key glycolytic enzymes). Key ScientificConcepts of Review: The working hypothesis of the manuscript proposes HIF-1a - the transcription factor critical for glucose metabolism of cancer cells regulated by PI3K/Akt pathway as an attractive target for application of flavonoids to mitigate cancer resistance. Phytochemicals represent a source of promising substances for cancer management applicable to primary, secondary, and tertiary care. However, accurate patient stratification and individualized patient profiling represent crucial steps in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM / 3PM). The article is focused on targeting molecular patterns by natural substances and provides evidence based recommendations for the 3PM relevant implementation.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Citovat

MAZURAKOVA, Alena; Lenka KOKLESOVA; Sandra Hurta CSIZMAR; Marek SAMEC; Aranka BROCKMUELLER; Miroslava SUDOMOVÁ; Kamil BIRINGER; Erik KUDELA; Martin PÉČ; Samson Mathews SAMUEL; Monika KASSAYOVA; Sherif T S HASSAN; Karel ŠMEJKAL; Mehdi SHAKIBAEI; Dietrich BUESSELBERG; Luciano SASO; Peter KUBATKA a Olga GOLUBNITSCHAJA. Significance of flavonoids targeting PI3K/Akt/HIF-1a signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine. Journal of Advanced Research. Amsterdam: Elsevier, 2024, roč. 55, neuvedeno, s. 103-118. ISSN 2090-1232. Dostupné z: https://doi.org/10.1016/j.jare.2023.02.015.

@article{2481979,
   author = {Mazurakova, Alena and Koklesova, Lenka and Csizmar, Sandra Hurta and Samec, Marek and Brockmueller, Aranka and Sudomová, Miroslava and Biringer, Kamil and Kudela, Erik and Péč, Martin and Samuel, Samson Mathews and Kassayova, Monika and Hassan, Sherif T S and Šmejkal, Karel and Shakibaei, Mehdi and Buesselberg, Dietrich and Saso, Luciano and Kubatka, Peter and Golubnitschaja, Olga},
   article_location = {Amsterdam},
   article_number = {neuvedeno},
   doi = {https://doi.org/10.1016/j.jare.2023.02.015},
   keywords = {Cancer; Resistance; Glycolysis; Flavonoids; predictive preventive personalized; medicine (PPPM / 3PM); Primary secondary tertiary care; Health-to-disease transition; WHO},
   language = {eng},
   issn = {2090-1232},
   journal = {Journal of Advanced Research},
   title = {Significance of flavonoids targeting PI3K/Akt/HIF-1a signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine},
   url = {https://pdf.sciencedirectassets.com/279952/1-s2.0-S2090123223X00149/1-s2.0-S2090123223000668/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEN7%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEaCXVzLWVhc3QtMSJHMEUCIAxfvcE3n%2FMXEBIZNhxPJO9N0qbH1Lv%2F9ytPPnv0l774AiEAhh1tecl},
   volume = {55},
   year = {2024}
}

TY  - JOUR
ID  - 2481979
AU  - Mazurakova, Alena - Koklesova, Lenka - Csizmar, Sandra Hurta - Samec, Marek - Brockmueller, Aranka - Sudomová, Miroslava - Biringer, Kamil - Kudela, Erik - Péč, Martin - Samuel, Samson Mathews - Kassayova, Monika - Hassan, Sherif T S - Šmejkal, Karel - Shakibaei, Mehdi - Buesselberg, Dietrich - Saso, Luciano - Kubatka, Peter - Golubnitschaja, Olga
PY  - 2024
TI  - Significance of flavonoids targeting PI3K/Akt/HIF-1a signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine
JF  - Journal of Advanced Research
VL  - 55
IS  - neuvedeno
SP  - 103-118
EP  - 103-118
PB  - Elsevier
SN  - 20901232
KW  - Cancer
KW  - Resistance
KW  - Glycolysis
KW  - Flavonoids
KW  - predictive preventive personalized
KW  - medicine (PPPM / 3PM)
KW  - Primary secondary tertiary care
KW  - Health-to-disease transition
KW  - WHO
UR  - https://pdf.sciencedirectassets.com/279952/1-s2.0-S2090123223X00149/1-s2.0-S2090123223000668/main.pdf?X-Amz-Security-Token=IQoJb3JpZ2luX2VjEN7%2F%2F%2F%2F%2F%2F%2F%2F%2F%2FwEaCXVzLWVhc3QtMSJHMEUCIAxfvcE3n%2FMXEBIZNhxPJO9N0qbH1Lv%2F9ytPPnv0l774AiEAhh1tecl
N2  - Background: Cancer management faces multiple obstacles, including resistance to current therapeutic approaches. In the face of challenging microenvironments, cancer cells adapt metabolically to maintain their supply of energy and precursor molecules for biosynthesis and thus sustain rapid proliferation and tumor growth. Among the various metabolic adaptations observed in cancer cells, the altered glucose metabolism is the most widely studied. The aberrant glycolytic modification in cancer cells has been associated with rapid cell division, tumor growth, cancer progression, and drug resistance. The higher rates of glycolysis in cancer cells, as a hallmark of cancer progression, is modulated by the transcription factor hypoxia inducible factor 1 alpha (HIF-1a), a downstream target of the PI3K/Akt signaling, the most deregulated pathway in cancer.Aim of Review: We provide a detailed overview of current, primarily experimental, evidence on the potential effectiveness of flavonoids to combat aberrant glycolysis-induced resistance of cancer cells to conventional and targeted therapies. The manuscript focuses primarily on flavonoids reducing cancer resistance via affecting PI3K/Akt, HIF-1a (as the transcription factor critical for glucose metabolism of cancer cells that is regulated by PI3K/Akt pathway), and key glycolytic mediators downstream of PI3K/Akt/HIF-1a signaling (glucose transporters and key glycolytic enzymes). Key ScientificConcepts of Review: The working hypothesis of the manuscript proposes HIF-1a - the transcription factor critical for glucose metabolism of cancer cells regulated by PI3K/Akt pathway as an attractive target for application of flavonoids to mitigate cancer resistance. Phytochemicals represent a source of promising substances for cancer management applicable to primary, secondary, and tertiary care. However, accurate patient stratification and individualized patient profiling represent crucial steps in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM / 3PM). The article is focused on targeting molecular patterns by natural substances and provides evidence based recommendations for the 3PM relevant implementation.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
ER  -

MAZURAKOVA, Alena; Lenka KOKLESOVA; Sandra Hurta CSIZMAR; Marek SAMEC; Aranka BROCKMUELLER; Miroslava SUDOMOVÁ; Kamil BIRINGER; Erik KUDELA; Martin PÉČ; Samson Mathews SAMUEL; Monika KASSAYOVA; Sherif T S HASSAN; Karel ŠMEJKAL; Mehdi SHAKIBAEI; Dietrich BUESSELBERG; Luciano SASO; Peter KUBATKA a Olga GOLUBNITSCHAJA. Significance of flavonoids targeting PI3K/Akt/HIF-1a signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine. \textit{Journal of Advanced Research}. Amsterdam: Elsevier, 2024, roč.~55, neuvedeno, s.~103-118. ISSN~2090-1232. Dostupné z: https://doi.org/10.1016/j.jare.2023.02.015.

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