Oxaliplatin disrupts nucleolar function through biophysical disintegration.
Cell Rep
; 41(6): 111629, 2022 11 08.
Article
in En
| MEDLINE
| ID: mdl-36351392
ABSTRACT
Platinum (Pt) compounds such as oxaliplatin are among the most commonly prescribed anti-cancer drugs. Despite their considerable clinical impact, the molecular basis of platinum cytotoxicity and cancer specificity remain unclear. Here we show that oxaliplatin, a backbone for the treatment of colorectal cancer, causes liquid-liquid demixing of nucleoli at clinically relevant concentrations. Our data suggest that this biophysical defect leads to cell-cycle arrest, shutdown of Pol I-mediated transcription, and ultimately cell death. We propose that instead of targeting a single molecule, oxaliplatin preferentially partitions into nucleoli, where it modifies nucleolar RNA and proteins. This mechanism provides a general approach for drugging the increasing number of cellular processes linked to biomolecular condensates.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Platinum
/
Antineoplastic Agents
Language:
En
Journal:
Cell Rep
Year:
2022
Document type:
Article