[Pd(<i>dach</i>)Cl<sub>2</sub>] Complex Targets Proteins Involved in Ribosomal Biogenesis, and RNA Splicing in HeLa Cells

This study aims to investigate the effect of the Pd(II) complex on HeLa cells using computational biology and proteomic analysis. [Pd(<i>dach</i>)Cl<sub>2</sub>]-treated HeLa cells were subjected to comparative proteomics analysis using label-free data-independent liquid chro...

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Main Authors: Vanja Ralić, Katarina Davalieva, Branislava Gemović, Milan Senćanski, Maja D. Nešić, Jelena Žakula, Milutin Stepić, Marijana Petković
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Inorganics
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Online Access:https://www.mdpi.com/2304-6740/13/7/215
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Summary:This study aims to investigate the effect of the Pd(II) complex on HeLa cells using computational biology and proteomic analysis. [Pd(<i>dach</i>)Cl<sub>2</sub>]-treated HeLa cells were subjected to comparative proteomics analysis using label-free data-independent liquid chromatography-tandem mass spectrometry (LC-MS/MS). In parallel, the informational spectrum method (ISM) was used to predict potential protein interactors of the [Pd(<i>dach</i>)Cl<sub>2</sub>] complex in HeLa cells. Proteomics analysis revealed 121 differentially abundant proteins (DAPs). Enrichment analysis of Gene Ontology (GO) annotations revealed ATP hydrolysis and RNA/protein binding as the top molecular functions and RNA splicing and protein–RNA complex organization as the top biological processes. Enrichment analysis of altered canonical pathways pointed out spliceosome and ribosome pathways. The top hub proteins with potential regulatory importance encompassed ribosomal proteins, translational and transcriptional factors, and components of the ribosome assembly machinery. ISM and cross-spectral analysis identified the nucleoplasm and sensor of the single-stranded DNA (SOSS DNA) complex. Proteome analysis showed that [Pd(<i>dach</i>)Cl<sub>2</sub>] targets proteins involved in ribosomal biogenesis and RNA splicing, whereas theoretical prediction implies also potential effect on p53 signaling pathway, and thus, alterations of the expression of regulatory proteins involved in cell survival and proliferation. These findings underscore the potential of Pd(II) complexes as anti-cancer agents, warranting further exploration and detailed functional validation.
ISSN:2304-6740