Unveiling the role of Ndrg1 gene on the oxidative stress induction behind the anticancer potential of styrylquinazoline derivatives
Abstract This work presents a multifaceted mechanism of the anticancer action of a 2-styrylquinazoline derivative. Extensive analysis of various aspects related to tyrosine kinase inhibition and effects on cellular targets at both the gene and protein levels revealed the potential of this IS20 compo...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-99277-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849312073740189696 |
|---|---|
| author | Katarzyna Malarz Michał Kuczak Patryk Rurka Patrycja Rawicka Anna Boguszewska-Czubara Josef Jampilek Jacek Mularski Robert Musiol Anna Mrozek-Wilczkiewicz |
| author_facet | Katarzyna Malarz Michał Kuczak Patryk Rurka Patrycja Rawicka Anna Boguszewska-Czubara Josef Jampilek Jacek Mularski Robert Musiol Anna Mrozek-Wilczkiewicz |
| author_sort | Katarzyna Malarz |
| collection | DOAJ |
| description | Abstract This work presents a multifaceted mechanism of the anticancer action of a 2-styrylquinazoline derivative. Extensive analysis of various aspects related to tyrosine kinase inhibition and effects on cellular targets at both the gene and protein levels revealed the potential of this IS20 compound for future research. This study presents a detailed analysis of the relationship between ABL and SRC kinase affecting the inhibition of the EGFR/mTOR signaling pathway in a non-obvious manner. The study was supported by experiments using various molecular biology techniques to confirm the induction of oxidative stress, inhibition of the cell cycle in the G2/M phase and the triggering of cell death via both the apoptosis and autophagy pathways. The cell models included those with different p53 protein status, which affected the cellular response in the form of altered Ndrg1 expression. Finally, the appropriate physicochemical properties of IS20 for adequate bioavailability and toxicity to the body were observed in an in vivo model. |
| format | Article |
| id | doaj-art-0f300bc29b3545b2ad52652908751c81 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-0f300bc29b3545b2ad52652908751c812025-08-20T03:53:12ZengNature PortfolioScientific Reports2045-23222025-05-0115111910.1038/s41598-025-99277-1Unveiling the role of Ndrg1 gene on the oxidative stress induction behind the anticancer potential of styrylquinazoline derivativesKatarzyna Malarz0Michał Kuczak1Patryk Rurka2Patrycja Rawicka3Anna Boguszewska-Czubara4Josef Jampilek5Jacek Mularski6Robert Musiol7Anna Mrozek-Wilczkiewicz8Department of Systems Biology and Engineering, Silesian University of TechnologyInstitute of Chemistry, University of Silesia in KatowiceInstitute of Physics, University of Silesia in KatowiceInstitute of Physics, University of Silesia in KatowiceDepartment of Medical Chemistry, Medical University of LublinDepartment of Chemical Biology, Palacky University OlomoucInstitute of Chemistry, University of Silesia in KatowiceInstitute of Chemistry, University of Silesia in KatowiceDepartment of Systems Biology and Engineering, Silesian University of TechnologyAbstract This work presents a multifaceted mechanism of the anticancer action of a 2-styrylquinazoline derivative. Extensive analysis of various aspects related to tyrosine kinase inhibition and effects on cellular targets at both the gene and protein levels revealed the potential of this IS20 compound for future research. This study presents a detailed analysis of the relationship between ABL and SRC kinase affecting the inhibition of the EGFR/mTOR signaling pathway in a non-obvious manner. The study was supported by experiments using various molecular biology techniques to confirm the induction of oxidative stress, inhibition of the cell cycle in the G2/M phase and the triggering of cell death via both the apoptosis and autophagy pathways. The cell models included those with different p53 protein status, which affected the cellular response in the form of altered Ndrg1 expression. Finally, the appropriate physicochemical properties of IS20 for adequate bioavailability and toxicity to the body were observed in an in vivo model.https://doi.org/10.1038/s41598-025-99277-1Anticancer drugStyrylquinazolineOxidative stressIron chelatorNdrg1p53 protein |
| spellingShingle | Katarzyna Malarz Michał Kuczak Patryk Rurka Patrycja Rawicka Anna Boguszewska-Czubara Josef Jampilek Jacek Mularski Robert Musiol Anna Mrozek-Wilczkiewicz Unveiling the role of Ndrg1 gene on the oxidative stress induction behind the anticancer potential of styrylquinazoline derivatives Scientific Reports Anticancer drug Styrylquinazoline Oxidative stress Iron chelator Ndrg1 p53 protein |
| title | Unveiling the role of Ndrg1 gene on the oxidative stress induction behind the anticancer potential of styrylquinazoline derivatives |
| title_full | Unveiling the role of Ndrg1 gene on the oxidative stress induction behind the anticancer potential of styrylquinazoline derivatives |
| title_fullStr | Unveiling the role of Ndrg1 gene on the oxidative stress induction behind the anticancer potential of styrylquinazoline derivatives |
| title_full_unstemmed | Unveiling the role of Ndrg1 gene on the oxidative stress induction behind the anticancer potential of styrylquinazoline derivatives |
| title_short | Unveiling the role of Ndrg1 gene on the oxidative stress induction behind the anticancer potential of styrylquinazoline derivatives |
| title_sort | unveiling the role of ndrg1 gene on the oxidative stress induction behind the anticancer potential of styrylquinazoline derivatives |
| topic | Anticancer drug Styrylquinazoline Oxidative stress Iron chelator Ndrg1 p53 protein |
| url | https://doi.org/10.1038/s41598-025-99277-1 |
| work_keys_str_mv | AT katarzynamalarz unveilingtheroleofndrg1geneontheoxidativestressinductionbehindtheanticancerpotentialofstyrylquinazolinederivatives AT michałkuczak unveilingtheroleofndrg1geneontheoxidativestressinductionbehindtheanticancerpotentialofstyrylquinazolinederivatives AT patrykrurka unveilingtheroleofndrg1geneontheoxidativestressinductionbehindtheanticancerpotentialofstyrylquinazolinederivatives AT patrycjarawicka unveilingtheroleofndrg1geneontheoxidativestressinductionbehindtheanticancerpotentialofstyrylquinazolinederivatives AT annaboguszewskaczubara unveilingtheroleofndrg1geneontheoxidativestressinductionbehindtheanticancerpotentialofstyrylquinazolinederivatives AT josefjampilek unveilingtheroleofndrg1geneontheoxidativestressinductionbehindtheanticancerpotentialofstyrylquinazolinederivatives AT jacekmularski unveilingtheroleofndrg1geneontheoxidativestressinductionbehindtheanticancerpotentialofstyrylquinazolinederivatives AT robertmusiol unveilingtheroleofndrg1geneontheoxidativestressinductionbehindtheanticancerpotentialofstyrylquinazolinederivatives AT annamrozekwilczkiewicz unveilingtheroleofndrg1geneontheoxidativestressinductionbehindtheanticancerpotentialofstyrylquinazolinederivatives |