Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Pharmacology and Toxicology, MS
Gupta, Ramesh C.
Committee Co-Chair (if applicable)
Egilmez, Nejat K.
Egilmez, Nejat K.
Hein, David W.
Schultz, David J.
Sharma, Vivek R.
colon; cancer; familial adenomatous polyposis; anthocyanidin; exosome
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths within the United States. Familial adenomatous polyposis (FAP) is an inherited disorder which if left untreated will develop into colon cancer. The family of plant-derived compounds, anthocyanins, show significant therapeutic potential against a variety of diseases, however, they are limited by their instability and poor bioavailability. The goal of my Master’s research project was to determine whether anthocyanidins (non-glycosylated anthocyanins) are more effective than the native anthocyanins, and whether exosomal formulation of anthocyanidins (ExoAnthos) can enhance therapeutic potency compared with free Anthos against both FAP and CRC. The antiproliferative effects of the native mixture of Anthos isolated from bilberry, with and without exosomal formulation, as well as individual Anthos against APC mutant (HT-29, Caco2), APC wild-type (HCT116) colon cancer cells and CCD-18Co normal colon cells were assessed using an MTT assay. To assess chemopreventive effects, the impact of the Anthos on polyp number was investigated in the APCMin/+ mouse model for FAP. While therapeutic efficacy of the Anthos treatment on colorectal tumor number was assessed in vivo using an APCMin/+ ETBF mouse tumor model. Early mechanistic work was undertaken to assess the impact of Anthos treatment on EGFR and Src phosphorylation using western blot analysis. Antiproliferation studies showed that ExoAnthos significantly lowered the IC50 compared to free Anthos against colon cancer cells. Anthos treatment led to significant reductions in polyp and tumor counts in vivo. Reduced Src and EGFR phosphorylation was also observed. These results provide a promising outlook on the future of the berry Anthos for treatment and prevention for both FAP and CRC.
Mudd, Ashley M., "Prevention and treatment of familial adenomatous polyposis and colorectal cancer by bilberry-derived anthocyanidins." (2017). Electronic Theses and Dissertations. Paper 2801.