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Review
. 2025 Apr 17;13(4):981.
doi: 10.3390/biomedicines13040981.

Pt(IV) Complexes as Anticancer Drugs and Their Relationship with Oxidative Stress

Vlad Iova  1 , Radu Ciprian Tincu  1   2 , Ioana Scrobota  3 , Mihail Silviu Tudosie  1   2
Affiliations
Review

Pt(IV) Complexes as Anticancer Drugs and Their Relationship with Oxidative Stress

Vlad Iova et al. Biomedicines. .

Abstract

Despite continuous research, cancer is still a leading cause of death worldwide; therefore, new methods of cancer management improvement are emerging. It is well known that in the pathophysiology of cancer, oxidative stress (OS) is a significant factor. Nevertheless, there is currently no quick or easy way to identify OS in cancer patients using blood tests. Currently, in cancer treatments, Pt(IV) complexes are preferred to Pt(II) complexes in terms of adverse effects, drug resistance, and administration methods. Intracellular reductants convert Pt(IV) complexes to their Pt(II) analogs, which are Pt compounds with anti-carcinogenic effects. Our aim was to find out if Pt(IV) complexes could be used to assess blood oxidative stress indicators and, consequently, monitor the development of cancer. In this review, we analyzed previous research using the PubMed and Google Scholar public databases to verify the potential use of Pt(IV) complexes in cancer management. We found that two main serum antioxidants, glutathione and ascorbic acid, which are easily measured using conventional methods, react favorably with Pt(IV) complexes. Our research results suggest Pt(IV) complexes as therapeutic anticancer drugs and potential diagnosis agents. However, further research must be conducted to verify this hypothesis.

Keywords: Pt(IV); anticancer prodrugs; ascorbic acid; cancer; glutathione; oxidative stress.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Effects of physiological and pathological OS.
Figure 2
Figure 2
The structures of Pt anticancer drugs: (a) cisplatin; (b) tetrachloro(DL-trans-1,2-diaminocyclohexane)platinum(IV) or ormaplatin/tetraplatin; (c) cis,cis,trans-[Pt(i-PrNH2)2Cl2(OH)2] or iproplatin; (d) cis,cis,trans-[Pt(NH3)2Cl2(OH)2] or oxoplatin.
Figure 3
Figure 3
Pt(IV) intracellular reduction mechanism and properties given to the prodrugs by the type of ligands.
Figure 4
Figure 4
Second-order rate constants k′ as a function of pH at 25.0 °C and μ = 1.0 M for the reduction of cis,trans-[Pt(cbdca)(NH3)2Cl2] by GSH (adapted from [246]).
Figure 5
Figure 5
Reaction mechanism proposed for the reduction of cis, trans-[Pt(cbdca)(NH3)2Cl2] by GSH (adapted from [246]).
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