Publications

Publications

Small Molecule Inhibitors of ERCC1-XPF Protein-Protein Interaction Synergize Alkylating Agents in Cancer Cells

By:
Contributors: Jack Tuszynski Research Group
Mol Pharmacol. 2013 Jul;84(1):12-24. doi: 10.1124/mol.112.082347. Epub 2013 Apr 11.

Abstract

The benefit of cancer chemotherapy based on alkylating agents is limited because of the action of DNA repair enzymes, which mitigate the damage induced by these agents. The interaction between the proteins ERCC1 and XPF involves two major components of the nucleotide excision repair pathway. Here, novel inhibitors of this interaction were identified by virtual screening based on available structures with use of the National Cancer Institute diversity set and a panel of DrugBank small molecules. Subsequently, experimental validation of the in silico screening was undertaken. Top hits were evaluated on A549 and HCT116 cancer cells. In particular, the compound labeled NSC 130813 [4-[(6-chloro-2-methoxy-9-acridinyl)amino]-2-[(4-methyl-1-piperazinyl)methyl]] was shown to act synergistically with cisplatin and mitomycin C; to increase UVC-mediated cytotoxicity; to modify DNA repair as indicated by the staining of phosphorylated H2AX; and to disrupt interaction between ERCC1 and XPF in cells. In addition, using the Biacore technique, we showed that this compound interacts with the domain of XPF responsible for interaction with ERCC1. This study shows that small molecules targeting the protein-protein interaction of ERCC1 and XPF can be developed to enhance the effects of alkylating agents on cancer cells.

 

PubMed

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APCaRI Registry and Biorepository enrolls 1500th participant – 30% of our goal

We are pleased to announce that the Alberta Prostate Cancer Registry and Biorepository reached 30% of its accrual goal by enrolling participant 1,500! To date more than 100,000 biosamples are stored in the Canadian Research Biorepository along with comprehensive clinical data – all available for cutting edge research.

This was possible thanks to our wonderful team of clinical research personnel, clinicians and partners who have been working collaboratively to reach our goals!

If you are interested in accessing biospecimens or clinical information, let us know at catalina.vasquez@ualberta.ca

Samples available from participants with prostate cancer and age-matched men with negative biopsy
  • Serum (400uL/vial)
  • Plasma (400uL/vial)
  • Buffy Coat (~300uL/vial)
  • Red Blood Cells (400uL/vial)
  • Urine (400uL/vial)
  • Semen (~400uL/vial)
Clinical Information available
  • Demographic information and co-morbidities
  • Family history of prostate cancer
  • Pathology and diagnosis details
  • Clinical and pathological staging
  • Treatment history
  • Outcomes
  • Biospecimen collection, sample availability and processing details
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