Date of Award

2022

Document Type

Thesis

Degree Name

Master of Science

College

College of Arts and Sciences

Program

Biology, MS

First Advisor

Denise Smith

Second Advisor

Desmond H. Murray

Third Advisor

Marlene Murray

Abstract

Glioblastoma (GBM) is the most common, lethal and aggressive brain tumor in adults. Standard treatment involves surgery, radiation therapy and temozolomide (TMZ) chemotherapy. However, GBM recurs and the average survival rate is between 12 to 18 months with 25% 1-year survival rate and 9% 5 years survival rate. Treatment options and advancement is limited by the blood brain barrier (BBB) which restricts drug entry into the brain and the immense heterogeneity of the tumor which limit adequate control of the entire tumor using one drug. In this research, we explored whether a combination mixture of TMZ and non-steroidal anti-inflammatory drugs (NSAIDs) which have shown anticancer properties (diclofenac, aspirin, ibuprofen, ketoprofen, naproxen, oxaproxin) may have synergistic or additive effects on U87MG cell line. All the combination mixtures in the ratio 1:1 had a lower LC50 value compared to individual compounds indicating that combination mixtures could have a synergistic or additive effect against GBM. We also examined whether novel hybrid of diclofenac (which had the lowest LC50 value, cell motility changes and morphological changes) and purines (which have shown to be able to enhance TMZ antitumor efficacy) could have a higher efficacy compared to individual compounds. All the novel hybrids of diclofenac and purines had lower LC50 compared to individual compounds. Therefore, hybrids and mixtures could have a higher efficacy and a better promise to GBM patients.

Subject Area

Temozolomide; Antineoplastic agents; Dicofenac; Glioblastoma multiforme

DOI

https://dx.doi.org/10.32597/theses/196/

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