[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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MDPI AG
2025-06-01
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| Online Access: | https://www.mdpi.com/2304-6740/13/7/215 |
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| author | Vanja Ralić Katarina Davalieva Branislava Gemović Milan Senćanski Maja D. Nešić Jelena Žakula Milutin Stepić Marijana Petković |
| author_facet | Vanja Ralić Katarina Davalieva Branislava Gemović Milan Senćanski Maja D. Nešić Jelena Žakula Milutin Stepić Marijana Petković |
| author_sort | Vanja Ralić |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cfd84b7930d44d148dc4607a40d78f2e |
| institution | DOAJ |
| issn | 2304-6740 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Inorganics |
| spelling | doaj-art-cfd84b7930d44d148dc4607a40d78f2e2025-08-20T03:08:01ZengMDPI AGInorganics2304-67402025-06-0113721510.3390/inorganics13070215[Pd(<i>dach</i>)Cl<sub>2</sub>] Complex Targets Proteins Involved in Ribosomal Biogenesis, and RNA Splicing in HeLa CellsVanja Ralić0Katarina Davalieva1Branislava Gemović2Milan Senćanski3Maja D. Nešić4Jelena Žakula5Milutin Stepić6Marijana Petković7COHERENCE Centre, Department of Atomic Physics, VINČA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaResearch Centre for Genetic Engineering and Biotechnology “Georgi D Efremov”, Macedonian Academy of Sciences and Arts, 1000 Skopje, North MacedoniaDepartment for Bioinformatics and Computational Chemistry, VINČA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaDepartment for Bioinformatics and Computational Chemistry, VINČA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaCOHERENCE Centre, Department of Atomic Physics, VINČA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Molecular Biology and Endocrinology, VINČA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaCOHERENCE Centre, Department of Atomic Physics, VINČA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaCOHERENCE Centre, Department of Atomic Physics, VINČA Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaThis 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.https://www.mdpi.com/2304-6740/13/7/215Pd(II) complexHeLa cervical cancer cellsproteomicsbioinformaticsspliceosomeribosome |
| spellingShingle | Vanja Ralić Katarina Davalieva Branislava Gemović Milan Senćanski Maja D. Nešić Jelena Žakula Milutin Stepić Marijana Petković [Pd(<i>dach</i>)Cl<sub>2</sub>] Complex Targets Proteins Involved in Ribosomal Biogenesis, and RNA Splicing in HeLa Cells Inorganics Pd(II) complex HeLa cervical cancer cells proteomics bioinformatics spliceosome ribosome |
| title | [Pd(<i>dach</i>)Cl<sub>2</sub>] Complex Targets Proteins Involved in Ribosomal Biogenesis, and RNA Splicing in HeLa Cells |
| title_full | [Pd(<i>dach</i>)Cl<sub>2</sub>] Complex Targets Proteins Involved in Ribosomal Biogenesis, and RNA Splicing in HeLa Cells |
| title_fullStr | [Pd(<i>dach</i>)Cl<sub>2</sub>] Complex Targets Proteins Involved in Ribosomal Biogenesis, and RNA Splicing in HeLa Cells |
| title_full_unstemmed | [Pd(<i>dach</i>)Cl<sub>2</sub>] Complex Targets Proteins Involved in Ribosomal Biogenesis, and RNA Splicing in HeLa Cells |
| title_short | [Pd(<i>dach</i>)Cl<sub>2</sub>] Complex Targets Proteins Involved in Ribosomal Biogenesis, and RNA Splicing in HeLa Cells |
| title_sort | pd i dach i cl sub 2 sub complex targets proteins involved in ribosomal biogenesis and rna splicing in hela cells |
| topic | Pd(II) complex HeLa cervical cancer cells proteomics bioinformatics spliceosome ribosome |
| url | https://www.mdpi.com/2304-6740/13/7/215 |
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