Burns, Colin SandersonHalatek, David2023-06-052023-06-052023-052023-04-28May 2023http://hdl.handle.net/10342/12851Colorectal cancer is the fourth most common cancer diagnosis per year as well as the fourth highest rate of death per year according to the Centers for Disease Control. Approximately 1/3rd of the diagnosed colorectal cancer cases per year will result in death. Prior research from our group has shown that the prostaglandin-ethanolamide 15-deoxy, [delta]12,14 prostamide J2 (15d-[delta]12,14-PMJ₂) is selectively toxic to murine melanoma cells (B16F10) and murine colorectal cells (CT-26) both in vitro and in vivo and significantly reduces tumor growth. Further, 15d-[delta]12,14-PMJ₂ induces cell death in primary patient melanoma cells and thus may be a promising therapeutic. As 15d-[delta]12,14-PMJ₂ can be made by the condensation of ethanolamine with 15-deoxy, [delta]12,14 prostaglandin J₂ (15d-[delta]12,14-PGJ₂), we sought to test the cytotoxicity of other prostamide derivatives to determine the structural features required for activity. Based on prior results in a study of related prodrugs, 15d-[delta]12,14-PMJ₂-Arvanil was selected as the top candidate for testing anti-cancer activity. After testing in both a human and murine cell line, it was determined that 15d-[delta]12,14-PMJ₂-Arvanil was not as cytotoxic as 15d-[delta]12,14-PMJ₂. It is possible that the bulkier functional group on the [alpha]-chain of the prostamide prevents transport into the cell the same way or to the same degree 15d-[delta]12,14-PMJ₂ enters. In an effort to test this hypothesis, and to develop an improved means for systemic delivery for this class of hydrophobic prostamides, engineered micelles composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] and D-[alpha]-tocopherol polyethylene glycol 1000 succinate were investigated as drug carriers.application/pdfenCancer TherapeuticsSmall MoleculeProstamideAnandamideProstaglandinJ-series ProstaglandinsJ-seriesCancer--TreatmentColon (Anatomy)--Cancer--TreatmentRectum--Cancer--TreatmentMaster's Thesis2023-06-02