Date of Graduation

5-2025

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Muldoon, Timothy

Abstract

Cancer is a result of uncontrolled growth and reproduction of cells. Damaged or abnormal cells grow and multiply when they should not and in turn the cells continue to proliferate and metastasize. Malignant cells rely on functional mitochondria for proliferation, metastasis, and survival. These mitochondria maintain a functional mitochondrial network through a quality control mechanism called mitophagy. Mitophagy is a conserved intracellular process to maintain quality control and remove damaged mitochondria.

Previous research has been done to examine the effects of mitophagy in tumor cells, as well as the effects of mitophagy inhibition. One focus of current research has been to examine the effects of chemosensitivity while inhibiting mitochondrial mitophagy. Chemotherapy resistance has been shown to be a major challenge in cancer therapy. Chemotherapeutic agents typically induce mitochondrial dysfunction with an increase in ROS generation. Chemotherapy increases mitophagy in order to exacerbate cytotoxic effects on cancer cells because excessive mitophagy induction can lead to loss of functional mitochondria and in turn, lead to cell death. Inhibition of mitophagy may help downregulate the resistance of drugs and chemotherapy in cancer cells. The microenvironment plays a role in mitophagy activation and levels of mitophagy.

The goal of this project is to examine the effects of mitophagy inhibition within two murine cancer cell lines during chemotherapy. More specifically, this project will test the mitophagy inhibitor, Liensinine, in combination with a chemotherapy agent, 5-fluorouracil (5-FU) in two cancer cell lines to determine its effect on mitophagy. The goal is to determine how these strategies and methods affect mitophagy levels, along with chemosensitivity and ROS levels.

Keywords

Mitophagy; Cancer Cells; MitoSOX Red; Fiji; Chemotherapy resistance

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