Jump to main content
Jump to site search


Organometallic ruthenium anticancer complexes inhibit human peroxiredoxin I activity by binding to and inducing oxidation of its catalytic cysteine residue

Author affiliations

Abstract

Peroxiredoxins (Prxs) are a family of ubiquitous antioxidant proteins and the inhibition of Prxs would elevate the reactive oxygen species level so as to induce cancer cell death. The interactions of organometallic ruthenium arene anticancer complexes with proteins play important roles in their mechanisms of action. Herein, we demonstrate that Ru complexes [(η6-arene)Ru(en)Cl]+ (en = ethylenediamine, arene = p-cymene (1), biphenyl (2) and 9,10-dihydrophenanthrene (3)) can inhibit the enzymatic activity of human peroxiredoxin I (Prx-I) in an order of 1 > 3 > 2. Mass spectrometric (MS) analysis revealed that 1–3 coordinated to the catalytic site Cys173 of Prx-I, and partially induced the oxidation of the thiolate to sulfenate. Quantitative MS analysis demonstrated that the higher level of the ruthenation of Cys173 is correlated with the higher inhibitory potency of the Ru complexes against Prx-I, suggesting their binding to Cys173 accounts for their inhibition towards Prx-I.

Graphical abstract: Organometallic ruthenium anticancer complexes inhibit human peroxiredoxin I activity by binding to and inducing oxidation of its catalytic cysteine residue

Back to tab navigation

Supplementary files

Publication details

The article was received on 06 Dec 2018, accepted on 17 Jan 2019 and first published on 17 Jan 2019


Article type: Paper
DOI: 10.1039/C8MT00352A
Citation: Metallomics, 2019, Advance Article

  •   Request permissions

    Organometallic ruthenium anticancer complexes inhibit human peroxiredoxin I activity by binding to and inducing oxidation of its catalytic cysteine residue

    Y. Lin, J. Wang, W. Zheng, Q. Luo, K. Wu, J. Du, Y. Zhao and F. Wang, Metallomics, 2019, Advance Article , DOI: 10.1039/C8MT00352A

Search articles by author

Spotlight

Advertisements