ArticleMolecular cancer2008
Phenylbutyrate interferes with the Fanconi anemia and BRCA pathway and sensitizes head and neck cancer cells to cisplatin.
Article in Molecular cancer, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Sodium Phenylbutyrate Attenuates Cisplatin-Induced Acute Kidney Injury Through Inhibition of Pyruvate Dehydrogenase Kinase 4.Biomedicines · 2024Article
- Drug resistance in ovarian cancer: from mechanism to clinical trial.Molecular cancer · 2024Review
- Influence of the Fatty Acid Metabolism on the Mode of Action of a Cisplatin(IV) Complex with Phenylbutyrate as Axial Ligands.Pharmaceutics · 2023Article
- Review
- Review
- Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy.International journal of molecular sciences · 2021Review
- Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach.International journal of molecular sciences · 2020Review
- Fanconi Anemia DNA Repair Pathway as a New Mechanism to Exploit Cancer Drug Resistance.Mini reviews in medicinal chemistry · 2020Review
- Inhibitors of the Fanconi anaemia pathway as potential antitumour agents for ovarian cancer.Exploration of targeted anti-tumor therapy · 2020Review
- DNA repair pathways and cisplatin resistance: an intimate relationship.Clinics (Sao Paulo, Brazil) · 2018Review
- Review
- DNA damage response and cancer therapeutics through the lens of the Fanconi Anemia DNA repair pathway.Cell communication and signaling : CCS · 2017Review
- The functional status of DNA repair pathways determines the sensitization effect to cisplatin in non-small cell lung cancer cells.Cellular oncology (Dordrecht, Netherlands) · 2016Article
- The multifaceted influence of histone deacetylases on DNA damage signalling and DNA repair.Nucleic acids research · 2016Review
- A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.Journal of biomolecular screening · 2016Article
- Pt(iv) derivatives of cisplatin and oxaliplatin with phenylbutyrate axial ligands are potent cytotoxic agents that act by several mechanisms of action.Chemical science · 2016Article
- Celastrol induces proteasomal degradation of FANCD2 to sensitize lung cancer cells to DNA crosslinking agents.Cancer science · 2015Article
- Curcumin reverses cisplatin resistance in cisplatin-resistant lung caner cells by inhibiting FA/BRCA pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Influence of PJ34 on the genotoxicity induced by melphalan in human multiple myeloma cells.Archives of medical science : AMS · 2015Article
- Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET.Nuclear medicine and biology · 2013Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCisplatin has been widely used to treat head and neck cancer. One of the clinical limitations with this treatment, however, is that tumors that are initially responsive to cisplatin later acquire resistance. We have recently shown that a subset of head and neck cancer cell lines has a defective Fanconi anemia DNA damage response pathway and this defect correlates to cisplatin sensitivity. We have also shown that the histone deacetylase inhibitor phenylbutyrate sensitize human cells to cisplatin. In this study we explored whether phenylbutyrate may sensitize head and neck cancer cells by interfering with the Fanconi anemia pathway.
resultsWe found that the phenylbutyrate sensitizes head and neck cancer cell lines to cisplatin. This sensitization by phenylbutyrate correlated to a significant decrease in the formation of cisplatin-induced FANCD2 nuclear foci, which is a functional read out of the Fanconi anemia and BRCA (FA/BRCA) pathway. This abrogation of the FA/BRCA pathway by phenylbutyrate was not due to loss of FANCD2 monoubiquitylation but rather correlated to a phenylbutyrate-mediated reduction in the expression of the BRCA1 protein. Furthermore, we found that cancer cells defective in the FA pathway were also sensitized to cisplatin by phenylbutyrate suggesting that phenylbutyrate targets additional pathways.
conclusionThe results from this study suggest that phenylbutyrate may have therapeutic utility as a cisplatin sensitizer in head and neck cancer by inhibiting the FA/BRCA pathway through the down regulation of BRCA1 as well as by an FA/BRCA-independent mechanism.
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