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Metal-Based Anticancer Complexes and p53: How Much Do We Know?

Samah Mutasim Alfadul1, Egor M Matnurov1, Alexander E Varakutin1

  • 1Drug Discovery Lab, Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Hong Kong SAR 999077, China.

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Summary

The tumor suppressor protein p53 is vital for genome stability but often mutated in cancer. This review explores how metals like zinc influence p53 function, potentially offering new cancer treatment strategies.

Keywords:
bioinorganiccopperironmetal anticancer complexesp53 familyplatinumrutheniumzinc

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Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • The p53 protein is crucial for genomic integrity and is frequently mutated in various cancers.
  • p53 family members, p63 and p73, also contribute to cancer development and progression.
  • Current therapeutic strategies involve organic molecules targeting wild-type or mutant p53 functions.

Purpose of the Study:

  • To investigate the role of metals in the structure and function of the p53 protein.
  • To explore the potential of metal-p53 interactions as a cancer vulnerability.
  • To review the effects of various metal complexes on p53 and its associated signaling pathways.

Main Methods:

  • Literature review focusing on the impact of metals on p53.
  • Analysis of studies detailing the dependence of wild-type p53 on zinc.
  • Examination of research on zinc supplementation restoring mutant p53 conformation.

Main Results:

  • Wild-type p53 protein function is dependent on the presence of zinc atoms.
  • Zinc supplementation can restore the altered conformation of mutant p53 protein.
  • Various metal complexes (Zn, Cu, Fe, Ru, Au, Ag, Pd, Pt, Ir, V, Mo, Bi, Sn) impact p53 protein and signaling.

Conclusions:

  • The interaction between p53 and metals, particularly zinc, presents a potential avenue for cancer therapy.
  • Metal-based compounds offer diverse mechanisms to modulate p53 activity in cancer.
  • Further research into metal-p53 interactions could lead to novel anti-cancer strategies.