Date on Master's Thesis/Doctoral Dissertation

8-2024

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Biology

Degree Program

Biology, PhD

Committee Chair

Schultz, David

Committee Co-Chair (if applicable)

Gupta, Ramesh

Committee Member

Menze, Michael

Committee Member

Perlin, Michael

Committee Member

Running, Mark

Author's Keywords

Phytochemistry; anticancer activity; breast cancer; drug delivery; exosomes; nanoparticle delivery

Abstract

Breast cancer (BC) is a leading contributor to the death of women and is the most common type of cancer. Many chemotherapy drugs are developed from plants, and some plant extracts can exhibit significant anticancer activities while also having less toxic side effects. The Apiaceae plant family consists of several species that are used as culinarily spices which have demonstrated antioxidant, chemopreventive, and anticancer activities. The encapsulation of anticancer phytochemicals into naturally produced membrane-bound nanoparticles known as exosomes could improve their systemic distribution and efficacy. Exosomes are involved in cell-to-cell communication through the delivery of proteins, nucleic acids, and small molecules. Bovine milk exosomes represent a scalable source of exosomes that are present in the human diet and have been explored as a drug delivery system that can increase effectiveness and improve bioavailability. To enhance the loading potential and bioactivity of Apiaceae phytochemicals, an acid hydrolysis (AH) of the glycoside compounds present was performed on eight Apiaceae spice extracts and the antiproliferative effects of AH-extracts and exosomal formulations were assayed. These treatments exhibited broad antiproliferative effects with lower IC50s in the exosomal formulations. The phytochemical contents of AH-cumin extracts and exosomal formulations were assayed with several methods, while the potential anticancer mechanisms of these treatments were investigated in triple negative BC (TNBC). AH-cumin extracts and exosomal formulations were shown to interact with multidrug resistance proteins and inhibit lipid metabolism in TNBC cells. AH-cumin extracts delivered through exosome nanoparticles represent a possible avenue towards the development of novel treatments for TNBC.

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