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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It’s Movember, time to Grow a Mo for a Bro!

It’s Movember, time to grow your moustache to raise funds and awareness of some serious health risks that men face, like suicide, testicular cancer and prostate cancer. Maybe growing a moustache isn’t your thing? No problem, host a Mo-ment for the men in your life instead!

APCaRI is a key stakeholder in the TrueNTH Global Registry; contributing 92% of the submitted patients in February 2018. Recently described by Evans et al., 2017 in an article published in BMJ Open, this project was established as an international registry with the goal to monitor the care of men with localised prostate cancer from 13 Movember-fundraising countries. Prostate cancer treatment and outcomes for men vary according to where they live, their race and the care they receive. The TrueNTH Global Registry is collecting a dataset based on the International Consortium for Health Outcome Measures (ICHOM) so we can better understand how to improve the care and treatment of men with localized prostate cancer, regardless of ethnicity and geography.

Please check out previous APCaRI blog posts that have talked about Movember (@Movember); the international Mens’ health Awareness charity, and about TrueNTH (@TrueNTH_Canada); a program funded by Prostate Cancer Canada (PCC) and the Movember Foundation that aims to improve the quality of life of men with prostate cancer and their families.

So start growing (or attach) your moustache today to raise funds and awareness to improve mens’ health!

- Perrin Beatty