Date of Award

8-2012

Degree Name

Doctor of Philosophy

Department

Chemistry

First Advisor

Dr. Ekkehard Sinn

Second Advisor

Dr. Sherine Obare

Third Advisor

Dr. Ramakrishna Guda

Fourth Advisor

Dr. Pamela Hoppe

Keywords

Anit-breast cancer, flavonoids, coumarins, modified gold-nanoparticples, estrogens, her-2

Abstract

Polyphenols compounds are abundant natural products found in many plants as secondary metabolites. These compounds display many interesting pharmacological activities, which have motivated chemists over the years to explore them, and their synthetic derivatives, as potential drugs, especially anticancer drugs. Breast cancer is the most common cancer in women globally, and in the United States of America the estimated worldwide new breast cancer cases and the number of deaths are 1.38 million and 458 thousand, respectively. Currently in the USA there are 2.6 million women who have been treated for breast cancer, and the estimated number of deaths are 39,520 in 2012. Therefore, this work focuses on investigating the anti-breast cancer activity of three groups of compounds: five naturally occurring flavonoids, five synthetic coumarins, and modified gold nanoparticles. Their pro-apoptotic activities were investigated and their toxicity on normal breast cells tested. The anti-breast cancer activity investigation used four breast carcinoma cell lines MDA-MB-231, MCF-7, BT-474, and SK-BR-3. The primary screening for their ER and HER-2 status indicated that only the MCF-7 and BT-474 cell lines are ER positive. Both BT-474 and SK-BR-3 express HER-2 protein. The anticancer activity assay MTT indicated that all the tested flavonoid compounds had anti-breast cancer activity and were not toxic on normal breast cells. The five synthetic coumarin compounds displayed variable toxicity from very toxic to moderately toxic. However, only two of them were not toxic to normal breast cells. Out of the third group of compounds, only one modified gold nanoparticle was promising as an anti-breast cancer agent without any toxicity against the normal breast cell. All of the promising anti-breast cancer agents were shown to have pro-apoptotic activities such as formation of apoptotic bodies and fragmentation of DNA.

Access Setting

Dissertation-Open Access

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Chemistry Commons

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