Characterization of the In Vivo Consequences of Salicylate Co-Administration on the Efficacy of Topoisomerase II Poison-Based Chemotherapy in a Model of Human Breast Cancer
Abstract
Human DNA topoisomerase IIα (TOP2A) is an essential enzyme that resolves the topological complexities of DNA, via transient DNA double-strand breaks (DSBs), during replication, transcription, and mitosis. Several gold-standard chemotherapeutics used for treating breast cancer are TOP2 poisons, which act by covalently trapping TOP2-DNA complexes leading to an accumulation of cytotoxic DNA DSBs. Salicylate, the primary metabolite of aspirin, catalytically inhibits DNA cleavage by TOP2A and is known to attenuate TOP2 poison cytotoxicity in MCF-7 breast cancer cells. Given, the widespread use of aspirin and other salicylate derivatives, determining their effects on chemotherapeutic efficacy could have far-reaching implications. To address this, a panel breast cancer cell lines was compiled to further characterize the effect of salicylate on TOP2 poison cytotoxicity. Following the in cyto work, a murine xenograft model of human breast cancer was used to evaluate the in vivo consequences of salicylate co-administration on TOP2 poison-based chemotherapy.
Description
Keywords
Animal Physiology, Biology--Cell, Biology--Molecular, Oncology, Pharmacology, Chemistry--Pharmaceutical
Citation
Crovetto, G. M. (2017). Characterization of the In Vivo Consequences of Salicylate Co-Administration on the Efficacy of Topoisomerase II Poison-Based Chemotherapy in a Model of Human Breast Cancer (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25293