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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Congratulations to top alumni honour awardee Dr. Ron Moore

Congratulations to Dr. Ron Moore, ’80 BSc, ’86 MD, ’91 PhD, who will receive an Alumni Honour Award from University of Alberta President David H. Turpin during the Alumni Awards Ceremony on Monday, Sept. 24, 2018, at the Northern Alberta Jubilee Auditorium in Edmonton.
The Alumni Honour Award recognizes the significant achievements and contributions by University of Alberta alumni to their profession and their community. Dr. Moore has made significant contributions to advancing our knowledge and treatment of bladder, kidney and prostate cancer. He has studied and developed laser treatment as therapy for prostate and bladder cancer, and developed new drugs to improve prostate cancer radiotherapy outcomes. Dr. Ron Moore has also actively mentored and trained hundreds of students throughout his career as well as serving on the APCaRI leadership committee.

The community is invited to celebrate as Dr. Ron Moore receives this top alumni award!
Date: Monday, Sept. 24, 2018
Location: Northern Alberta Jubilee Auditorium (11455 87 Ave), Edmonton, Alberta
Time: 7 p.m. ceremony with dessert reception to follow
Cost: Free, register for tickets
Dress: Business attire

For more information, please contact the Office of Alumni Relations at 780-492-3224, toll free 1-800-661-2593 or alumni@ualberta.ca
Featured at @UAlbertaAlumni and in the New Trail magazine.

- Perrin Beatty