ArticleInvestigational new drugs2014
PRIMA-1, a mutant p53 reactivator, induces apoptosis and enhances chemotherapeutic cytotoxicity in pancreatic cancer cell lines.
Article in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 69 citations in OpenAlex.
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- Activating p53Nature communications · 2026Article
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Effects of fecal microbiota transplantation on metabolic health of DBA mice.Frontiers in microbiology · 2024Article
- PRIMA-1ACS omega · 2023Article
- Anti-inflammatory effects of PRIMA-1Inflammopharmacology · 2023Article
- PRIMA-1 inhibits Y220C p53 amyloid aggregation and synergizes with cisplatin in hepatocellular carcinoma.Frontiers in molecular biosciences · 2023Article
- An EGFR/HER2-targeted conjugate sensitizes gemcitabine-sensitive and resistant pancreatic cancer through different SMAD4-mediated mechanisms.Nature communications · 2022Article
- Article
- APR-246-The Mutant TP53 Reactivator-Increases the Effectiveness of Berberine and Modified Berberines to Inhibit the Proliferation of Pancreatic Cancer Cells.Biomolecules · 2022Article
- APR-246 induces early cell death by ferroptosis in acute myeloid leukemia.Haematologica · 2022Article
- Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ).Nature communications · 2021Article
- Cell death in pancreatic cancer: from pathogenesis to therapy.Nature reviews. Gastroenterology & hepatology · 2021Review
- Mutations in key driver genes of pancreatic cancer: molecularly targeted therapies and other clinical implications.Acta pharmacologica Sinica · 2021Review
- An overview of genetic mutations and epigenetic signatures in the course of pancreatic cancer progression.Cancer metastasis reviews · 2021Review
- Antitumor Effects of PRIMA-1 and PRIMA-1Cells · 2021Review
- Novel ovarian cancer maintenance therapy targeted at mortalin and mutant p53.International journal of cancer · 2020Article
- Patient-specific logic models of signaling pathways from screenings on cancer biopsies to prioritize personalized combination therapies.Molecular systems biology · 2020Article
- Mutant p53 on the Path to Metastasis.Trends in cancer · 2020Review
- Therapeutic targeting of mutant p53 in pediatric acute lymphoblastic leukemia.Haematologica · 2020Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TP53 mutation is a common event in many cancers, including pancreatic adenocarcinoma, where it occurs in 50-70 % of cases. In an effort to reactivate mutant p53 protein, several new drugs are being developed, including PRIMA-1 and PRIMA-1(Met)/APR-246 (p53 reactivation and induction of massive apoptosis). PRIMA-1 has been shown to induce apoptosis in tumor cells by reactivating p53 mutants, but its effect in pancreatic cancer remains unclear. Here we investigated the effects of PRIMA-1 on cell viability, cell cycle and expression of p53-regulated proteins in PANC-1 and BxPC-3 (mutant TP53), and CAPAN-2 (wild-type TP53) pancreatic cell lines. Treatment with PRIMA-1 selectively induced apoptosis and cell cycle arrest in p53 mutant cells compared to CAPAN-2 cells. The growth suppressive effect of PRIMA-1 was markedly reduced in p53 mutant cell lines transfected with p53 siRNA, supporting the role of mutant p53 in PRIMA-1 induced cell death. Moreover, treatment with the thiol group donor N-acetylcysteine completely blocked PRIMA-1-induced apoptosis and reinforced the hypothesis that thiol modifications are important for PRIMA-1 biological activity. In combination treatments, PRIMA-1 enhanced the anti-tumor activity of several chemotherapic drugs against pancreatic cancer cells and also exhibited a pronounced synergistic effect in association with the Mdm2 inhibitor Nutlin-3. Taken together, our data indicate that PRIMA-1 induces apoptosis in p53 mutant pancreatic cancer cells by promoting the re-activation of p53 and inducing proapoptotic signaling pathways, providing in vitro evidence for a potential therapeutic approach in pancreatic cancer.
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