Label-Free Target Identification Reveals the Anticancer Mechanism of a Rhenium Isonitrile Complex

Elucidation of the molecular mechanism of therapeutic agents and potential candidates is in high demand. Interestingly, rhenium-based complexes have shown a highly selective anticancer effect, only on cancer cells, unlike platinum-based drugs, such as cisplatin and carboplatin. These differences mig...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in chemistry 2022-03, Vol.10, p.850638-850638
Main Authors: Yim, Junhyeong, Park, Seung Bum
Format: Article
Language:English
Subjects:
anticancer agents
Chemistry
heat shock protein 60
label-free target identification
metal-based drug
rhenium isonitrile complex
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Elucidation of the molecular mechanism of therapeutic agents and potential candidates is in high demand. Interestingly, rhenium-based complexes have shown a highly selective anticancer effect, only on cancer cells, unlike platinum-based drugs, such as cisplatin and carboplatin. These differences might be attributed to their different molecular targets. We confirmed that the target of tricarbonyl rhenium isonitrile polypyridyl (TRIP) complex is a protein, not DNA, using ICP-MS analysis and identified heat shock protein 60 (HSP60) as its target protein using a label-free target identification method. The subsequent biological evaluation revealed that TRIP directly inhibits the chaperone function of HSP60 and induces the accumulation of misfolded proteins in mitochondria, thereby leading to the activation of mitochondrial unfolded protein response (mtUPR)-mediated JNK2/AP-1/CHOP apoptotic pathway.
ISSN:2296-2646
2296-2646
DOI:10.3389/fchem.2022.850638