Data · study · 2026
A novel triple-action Pt(IV) prodrug presents multiple anti-cancer effects and overcomes cisplatin resistance [XR-seq]
Listed in NCBI GEO
Cisplatin is a widely used chemotherapeutic agent that is cytotoxic to cancer cells primarily by damaging their DNA.
Description
However, drug resistance limits its efficacy and significantly restricts its use. Cisplatin resistance is complex and multifactorial, as it involves numerous cellular pathways and activities.
Among these are the constitutive activation of the nuclear factor erythroid 2 (NF-E2)-related factor 2 / Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Nrf2/Keap1) pathway, overexpression of histone deacetylases (HDACs), and increased nucleotide excision repair (NER). Simultaneous inhibition of both the Nrf2/Keap1 pathway and HDAC activity could be beneficial for addressing the challenge of cisplatin resistance and retrieve chemo-sensitivity.
Read the rest (2 more)
In this study, we synthesized a novel Pt(IV) derivative that is assembled from cisplatin, an Nrf2 inhibitor, and an HDAC inhibitor. This triple-action prodrug, cct-[Pt(NH3)2Cl2(VPA)(PhB)] (cPVP), enabled the parallel-targeting of multiple cancer-related pathways using a single agent. Compared to cisplatin, cPVP exhibited significantly enhanced damage-formation and cytotoxicity, and presented inhibitory effects on the Nrf2/Keap1 pathway, HDAC activity, and NER.
Furthermore, the prodrug demonstrated improved efficacy against cisplatin-resistant cells. Most importantly, cPVP prevented the development of resistance to both cisplatin and itself in cancer cells. Together, our results suggest that the triple-action cPVP could be a feasible alternative to cisplatin in the clinic.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE243nnn/GSE243354 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE243354 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1017874 ncbi.nlm.nih.gov/bioproject/PRJNA1017874 ↗
project · from NCBI GEO
- PubMed 42072663 pubmed.ncbi.nlm.nih.gov/42072663 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Homo sapiens · Other
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE243354 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:other | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |