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

Kurz, EbbaCrovetto, Gina Marie Alexandra2017-02-022017-02-0220172017Crovetto, 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/25293http://hdl.handle.net/11023/3638Human 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.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Animal PhysiologyBiology--CellBiology--MolecularOncologyPharmacologyChemistry--PharmaceuticalTopoisomerase IIaSalicylateAcetylsalicylic AcidCancer BiologyXenograftDoxorubicinEtoposideCytotoxicityChemotherapyTranslational ResearchTOP2ACharacterization of the In Vivo Consequences of Salicylate Co-Administration on the Efficacy of Topoisomerase II Poison-Based Chemotherapy in a Model of Human Breast Cancermaster thesis10.11575/PRISM/25293