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A novel triple-action Pt(IV) prodrug presents multiple anti-cancer effects and overcomes cisplatin resistance

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE243355 | GEO | 2026/04/07

REPOSITORIES: GEO

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A novel triple-action Pt(IV) prodrug presents multiple anti-cancer effects and overcomes cisplatin resistance [XR-seq]

Project description:Cisplatin is a widely used chemotherapeutic agent that is cytotoxic to cancer cells primarily by damaging their DNA. 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. 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.

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Project description:A novel triple-action Pt(IV) prodrug presents multiple anti-cancer effects and overcomes cisplatin resistance

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Project description:A novel triple-action Pt(IV) prodrug presents multiple anti-cancer effects and overcomes cisplatin resistance [XR-seq]

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