Date of Graduation

Spring 2020

Degree

Master of Science in Biology

Department

Biology

Committee Chair

Kyoungtae Kim

Keywords

Saporin, Chlorotoxin, radioactive iodine resistance, thyroid cancer, MMP-2, ML-1, XTT, ROS, apoptosis, Cisplatin

Subject Categories

Alternative and Complementary Medicine | Cells | Endocrinology, Diabetes, and Metabolism | Medical Cell Biology | Medical Toxicology | Otorhinolaryngologic Diseases | Therapeutics

Abstract

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I hypothesize that Chlorotoxin-conjugated to Saporin (CTX-SAP) would impede the growth of aggressive thyroid cancer cell lines expressing MMP-2 receptors. Moreover, there is also an unmet need for better platinum-based anti-cancer drugs. Cisplatin, an FDA approved anti-cancer drug was tested alongside the novel cyanoximate, Pt (DECO)2 for its ability to reduce cell viability, reduce superoxide, and increase apoptosis. Results from my study support the potential of CTX-SAP, but offer limited availability for future study. My findings also demonstrate that Pt (DECO)2 is more effective at reducing cell viability, reactive oxygen species, and increasing apoptosis compared to Cisplatin.

Copyright

© Husref Rizvanovic

Available for download on Wednesday, May 12, 2021

Open Access

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