Amr Ezzat Mohamed Mahmoud

Doctoral Dissertation Announcement

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Candidate: Amr Ezzat Mohamed Mahmoud

Degree of: Doctor of Philosophy

Department: Chemistry

Title: Investigating the Biochemical Activity of Some Flavonoids, Coumarins and Modified Gold-Nanoparticles as Anti-Breast Cancer Agents

Committee:
Dr. Ekkehard Sinn, Chair
Dr. Sherine Obare
Dr. Ramakrishna Guda
Dr. Pamela Hoppe

Date: Friday, June 29, 2012 10:30 a.m. to 12:30 p.m.
1260 Chemistry Building

Abstract:
Polyphenolic 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 United States, 2.6 million women 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 containing five naturally occurring flavonoids, five synthetic coumarins, and modified gold nanoparticles. Their pro-apoptotic activities are investigated and their toxicity on normal breast cells is tested. The anti-breast cancer activity investigation carried on using 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 indicates that only the MCF-7 and BT-474 cell lines are ER positive. Both BT-474 and SK-BR-3 are positively expressing HER-2 protein. The anticancer activity assay MTT, indicates that all the tested flavonoid compounds have anti-breast cancer activity and are not toxic on normal breast cells. The five synthetic coumarin compounds display variable toxicity from very toxic to moderate. However, only two of them are not toxic on normal breast cells.  Out of the third group of compounds, only one modified gold nanoparticle is promising as an anti-breast cancer agent without any toxicity against the normal breast cell. All of the promising anti-breast cancer agents are shown to have pro-apoptotic activities such as formation of apoptotic bodies and fragmentation of DNA.