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Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer

Cancer is a major cause of death, affecting human life in both developed and developing countries. Numerous antitumor agents exist but their toxicity and low efficacy limits their utility. Furthermore, the complex pathophysiological mechanisms of cancer, serious side effects and poor prognosis restr...

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Autores principales: Rahman, Noor, Khan, Haroon, Zia, Asad, Khan, Asifullah, Fakhri, Sajad, Aschner, Michael, Gul, Karim, Saso, Luciano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582810/
https://www.ncbi.nlm.nih.gov/pubmed/34768743
http://dx.doi.org/10.3390/ijms222111315
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author Rahman, Noor
Khan, Haroon
Zia, Asad
Khan, Asifullah
Fakhri, Sajad
Aschner, Michael
Gul, Karim
Saso, Luciano
author_facet Rahman, Noor
Khan, Haroon
Zia, Asad
Khan, Asifullah
Fakhri, Sajad
Aschner, Michael
Gul, Karim
Saso, Luciano
author_sort Rahman, Noor
collection PubMed
description Cancer is a major cause of death, affecting human life in both developed and developing countries. Numerous antitumor agents exist but their toxicity and low efficacy limits their utility. Furthermore, the complex pathophysiological mechanisms of cancer, serious side effects and poor prognosis restrict the administration of available cancer therapies. Thus, developing novel therapeutic agents are required towards a simultaneous targeting of major dysregulated signaling mediators in cancer etiology, while possessing lower side effects. In this line, the plant kingdom is introduced as a rich source of active phytochemicals. The secondary metabolites produced by plants could potentially regulate several dysregulated pathways in cancer. Among the secondary metabolites, flavonoids are hopeful phytochemicals with established biological activities and minimal side effects. Flavonoids inhibit B-cell lymphoma 2 (Bcl-2) via the p53 signaling pathway, which is a significant apoptotic target in many cancer types, hence suppressing a major dysregulated pathway in cancer. To date, there have been no studies reported which extensively highlight the role of flavonoids and especially the different classes of flavonoids in the modulation of Bcl-2 in the P53 signaling pathway. Herein, we discuss the modulation of Bcl-2 in the p53 signaling pathway by different classes of flavonoids and highlight different mechanisms through which this modulation can occur. This study will provide a rationale for the use of flavonoids against different cancers paving a new mechanistic-based approach to cancer therapy.
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spelling pubmed-85828102021-11-12 Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer Rahman, Noor Khan, Haroon Zia, Asad Khan, Asifullah Fakhri, Sajad Aschner, Michael Gul, Karim Saso, Luciano Int J Mol Sci Review Cancer is a major cause of death, affecting human life in both developed and developing countries. Numerous antitumor agents exist but their toxicity and low efficacy limits their utility. Furthermore, the complex pathophysiological mechanisms of cancer, serious side effects and poor prognosis restrict the administration of available cancer therapies. Thus, developing novel therapeutic agents are required towards a simultaneous targeting of major dysregulated signaling mediators in cancer etiology, while possessing lower side effects. In this line, the plant kingdom is introduced as a rich source of active phytochemicals. The secondary metabolites produced by plants could potentially regulate several dysregulated pathways in cancer. Among the secondary metabolites, flavonoids are hopeful phytochemicals with established biological activities and minimal side effects. Flavonoids inhibit B-cell lymphoma 2 (Bcl-2) via the p53 signaling pathway, which is a significant apoptotic target in many cancer types, hence suppressing a major dysregulated pathway in cancer. To date, there have been no studies reported which extensively highlight the role of flavonoids and especially the different classes of flavonoids in the modulation of Bcl-2 in the P53 signaling pathway. Herein, we discuss the modulation of Bcl-2 in the p53 signaling pathway by different classes of flavonoids and highlight different mechanisms through which this modulation can occur. This study will provide a rationale for the use of flavonoids against different cancers paving a new mechanistic-based approach to cancer therapy. MDPI 2021-10-20 /pmc/articles/PMC8582810/ /pubmed/34768743 http://dx.doi.org/10.3390/ijms222111315 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Rahman, Noor
Khan, Haroon
Zia, Asad
Khan, Asifullah
Fakhri, Sajad
Aschner, Michael
Gul, Karim
Saso, Luciano
Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer
title Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer
title_full Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer
title_fullStr Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer
title_full_unstemmed Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer
title_short Bcl-2 Modulation in p53 Signaling Pathway by Flavonoids: A Potential Strategy towards the Treatment of Cancer
title_sort bcl-2 modulation in p53 signaling pathway by flavonoids: a potential strategy towards the treatment of cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582810/
https://www.ncbi.nlm.nih.gov/pubmed/34768743
http://dx.doi.org/10.3390/ijms222111315
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