Modulating the p53-MDM2 pathway

the therapeutic potential of natural compounds in cancer treatment

Authors

  • Iman Ramli Laboratory of Applied Biochemistry, Faculté des Sciences de la Nature et de la Vie, Université Constantine 1 Frères Mentouri, 25000 Constantine, Algeria https://orcid.org/0000-0002-3364-967X
  • Thamere Cheriet Unité de Valorisation des Ressources Naturelles, Molécules Bioactives et Analyses Physicochimiques et Biologiques, Université Constantine 1 Frères Mentouri, 25000 Constantine, Algeria; Département Science de la Nature et de la Vie, Faculté des Sciences Exactes et Science de la Nature et de la Vie, Université Mohammed Boudiaf-Oum El-Bouaghi, 04000 Oum El-Bouaghi, Algeria https://orcid.org/0000-0001-5305-1360
  • Anna Maria Posadino Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy https://orcid.org/0000-0002-6155-159X
  • Roberta Giordo Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy https://orcid.org/0000-0002-2187-4458
  • Grazia Fenu Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy https://orcid.org/0000-0002-1499-9869
  • Kingsley Chukwuemeka Nwachukwu Department of Microbiology, Faculty of Biological Sciences, Abia State University, Uturu, Nigeria; Covenant Applied Informatics Communication African Centre for Excellence (CApIC-ACE), Covenant University, Ota, Ogun State, Nigeria https://orcid.org/0000-0002-8527-2720
  • Oluwafemi Adebayo Oyewole Department of Microbiology, Federal University of Technology, Minna, Nigeria https://orcid.org/0000-0001-9470-8488
  • Charles Oluwaseun Adetunji Laboratory of Applied Microbiology, Biotechnology and Nanotechnology, Department of Microbiology, Edo State University, Uzairue, Edo State, Nigeria https://orcid.org/0000-0003-3524-6441
  • Daniela Calina Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania. E-mail: calinadaniela@gmail.com https://orcid.org/0000-0002-1523-9116
  • Javad Sharifi-Rad Universidad Espíritu Santo, Samborondón 092301, Ecuador. E-mail: javad.sharifirad@gmail.com https://orcid.org/0000-0002-7301-8151
  • Gianfranco Pintus Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43B, 07100 Sassari, Italy. E-mail: gpintus@uniss.it https://orcid.org/0000-0002-3031-7733

DOI:

https://doi.org/10.17179/excli2024-7791

Keywords:

p53, MDM2, cancer therapy, natural products, p53; MDM2; Cancer Therapy; Natural Products; Tumor Suppression

Abstract

The p53-MDM2 pathway plays a crucial role regulating tumor suppression and is a focal point of cancer research. This literature review delves into the complex interplay between the tumor suppressor protein p53 and its main regulator MDM2, highlighting their interaction and implications in cancer development and progression. The review compiles and summarizes the existing understanding of the biology and regulation of p53 and MDM2, emphasizing their roles in various cellular processes, including cell cycle regulation, DNA repair, apoptosis, and metabolism. It also discusses the disruption of the p53-MDM2 interaction in different cancer types and its impact on tumor progression and therapeutic resistance. Recent studies have highlighted natural products as promising avenues for targeting the p53-MDM2 pathway. This review categorizes these natural compounds into three groups based on their mechanisms: those that inhibit MDM2 expression or stability, those that prevent p53-MDM2 binding, and those that stabilize p53 by inhibiting MDM2’s E3 ligase activity. Detailed mechanisms of action, structural aspects, and potential therapeutic applications of various natural products, including polyphenols, terpenoids, and alkaloids, are presented. Despite significant advances in understanding the p53-MDM2 interaction and the identification of natural products capable of modulating this pathway, further research is necessary to evaluate the clinical efficacy, toxicity, and bioavailability of these compounds. The promising role of natural products in cancer therapy underscores the importance of ongoing investigation and development of these agents as potential treatments for cancer.

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Published

2024-11-22

How to Cite

Ramli, I., Cheriet, T., Posadino, A. M., Giordo, R., Fenu, G., Chukwuemeka Nwachukwu, K., … Pintus, G. (2024). Modulating the p53-MDM2 pathway: the therapeutic potential of natural compounds in cancer treatment. EXCLI Journal, 23, 1397–1439. https://doi.org/10.17179/excli2024-7791

Issue

Vol. 23 (2024)

Section

Review articles

Categories

License

Copyright (c) 2024 Iman Ramli, Thamere Cheriet, Anna Maria Posadino, Roberta Giordo, Grazia Fenu, Kingsley Chukwuemeka Nwachukwu, Oluwafemi Adebayo Oyewole, Charles Oluwaseun Adetunji, Daniela Calina, Javad Sharifi-Rad, Gianfranco Pintus

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