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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Annual Terwillegar Trail Run and Walk Fundraiser

It was a beautiful crisp fall morning for a 10 Km trail run or 7.5 Km walk through the Terwillegar ravine on Saturday, September 29th. The run/walk, hosted by the Terwillegar Trail Run/Walk and the Alberta Cancer Foundation,  is in its 7th year. Its goal is to bring families and friends together to enjoy the outdoors and ultimately raise funds for prostate cancer research.

John Lewis’ research group was out in force; represented by John Lewis, Catalina Vasquez, Arun Raturi, Perrin Beatty and Abbie Coros. Despite the fact that, as one of the run/walk organizers Doug Mitchell pointed out to the participants, John ran in 15-year-old tennis shoes, the Lewis group runners ran well and had a great time!

Funds raised by the Terwillegar Trail Run and Walk go to support cancer research in Alberta. Check out the Alberta Cancer Foundations’ “Dollars at Work” to read about how these funds have been used to support the research from APCaRI members Dr. Frank Wuest and Dr. John Lewis’ labs!

With just over 100 participants this year the 2018 Terwillegar Trail Run/Walk raised over $21 000 for prostate cancer research! You can still donate to this awesome fundraiser, just go to Alberta Cancer Foundation TTRW and click on the Donate Now button!

- Perrin Beatty