Title

Effectiveness and Mechanism of Action of Modified Porphyrins for Photodynamic Therapy of Triple Negative Breast Cancer Cells

Date of Award

2019

Document Type

Thesis

Department

Chemistry

First Advisor

Dr. Tim Hayes

Second Advisor

Dr. Tim Knight

Third Advisor

Dr. Benjamin Utter

Abstract

Triple negative breast cancer (TNBC) is a particularly aggressive form of breast cancer that lacks the three molecules typically targeted for treatment. Standard treatment methods leave much to be desired--the rates of metastasis and recurrence are high and the prognosis for most patients with TNBC is poor. One potential treatment for TNBC is photodynamic therapy (PDT), which uses compounds called photosensitizers that are taken up by all tissues in the body. The tumor is exposed to light, activating the photosensitizer and creating reactive oxygen species that cause cell death. This method is relatively pain-free, effective, and does not harm cells that are not exposed to light.

The goal of these experiments was to assess the effectiveness of porphyrin derivatives as PDT agents in vitro on MDA-MB231 triple-negative breast cancer cells. The polyhydroxy R-groups (e.g., H2TPP-3NH) produced LD50as of 40-50 µM and showed little to no dark toxicity.

For one compound, experiments were performed to determine the mechanism of cell death. A TUNEL assay was performed to measure DNA fragmentation, and the TUNEL-stained cells were co-stained with antibodies to help identify the method of cell death. Results indicated that the cells were dying primarily by caspase-mediated apoptosis.

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