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 at the Enbridge Ride to Conquer Cancer for second year

Well, we did it again!  Several APCaRI members participated in a 2-day major cycling event called the Enbridge Ride to Conquer Cancer, benefiting the Alberta Cancer Foundation. We cycled 228 kms over 2 days along the majestic Rockies with thousands of other Riders, supported by an amazing team of volunteers. Riding along with over 50 members of the Cross Cancer Institute Team, and 1402 riders in total, it was an epic experience!
Most importantly, we raised $6.35M to support cutting edge cancer research in Alberta. We are very thankful for the support we received, which will help us to beat prostate cancer.

If you didn’t get a chance to support one of our riders, please consider contributing to the team’s efforts at our DONATE page.

- Catalina Vasquez