Title
Interaction with Ribosomal Proteins Accompanies Stress Induction of the Anticancer Metallodrug BOLD‐100/KP1339 in the Endoplasmic Reticulum
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Abstract
The ruthenium-based anticancer agent BOLD-100/KP1339 has shown promising results in several in vitro and in vivo tumour models as well as in early clinical trials. However, its mode of action remains to be fully elucidated. Recent evidence identified stress induction in the endoplasmic reticulum (ER) and concomitant down-modulation of HSPA5 (GRP78) as key drug effects. By exploiting the naturally formed adduct between BOLD-100 and human serum albumin as an immobilization strategy, we were able to perform target-profiling experiments that revealed the ribosomal proteins RPL10, RPL24, and the transcription factor GTF2I as potential interactors of this ruthenium(III) anticancer agent. Integrating these findings with proteomic profiling and transcriptomic experiments supported ribosomal disturbance and concomitant induction of ER stress. The formation of polyribosomes and ER swelling of treated cancer cells revealed by TEM validated this finding. Thus, the direct interaction of BOLD-100 with ribosomal proteins seems to accompany ER stress-induction and modulation of GRP78 in cancer cells.
Keywords
bioinorganic chemistrymetals in medicinemulti-omicsribosomeruthenium
Object type
Language
English [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:1218253
Appeared in
Title
Angewandte Chemie International Edition
Volume
60
Issue
10
ISSN
1433-7851
Issued
2021
From page
5063
To page
5068
Publisher
Wiley
Date issued
2021
Access rights
Rights statement
© 2020 The Authors

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