Youssef Abdou

Abstract

Cancer is currently one of the leading causes of mortality and morbidity worldwide. Most anticancer therapies rely on small molecule drugs (<0.5 kDa). As with all small molecule drugs, chemotherapy is highly toxic and presents many off-target side effects. Peptide drugs offer improved specificity and are cheaper and more accessible to manufacture. In this study, we have developed a support vector machine (SVM) model in order to detect peptide sequences with potential anticancer activity through scanning the Red Sea Metagenomic library. Furthermore, we conducted an in silico study in order to analyze one of the peptides returned by the SVM pipeline and assessed its cytotoxicity and the mode of cell death by conducting MTT and Annexin V staining assays, respectively. We observed that the selected anticancer peptide contains the C-terminal portion of the homeodomain structure, of human Pax6, an antennapedia homeodomain region, and can bind DNA. Furthermore, we observed dose-response cytotoxicity of HepG2 cells with our peptide. No such cytotoxicity was observed in HeLa cells; a morphological change, however, was observed. We examined the cytotoxicity of our drug against 1BR-hTERT normal skin cells. Our peptide drug induced dose-dependent cytotoxicity that was markedly weaker than that of cancer treated cells. Together our data illustrates the isolation of one peptide drug candidate from the AUC Red Sea metagenomic library; furthermore, we were able to observe the selective dose-dependent reduction of HepG2 cell viability

Department

Biotechnology Program

Degree Name

MS in Biotechnology

Graduation Date

2-1-2016

Submission Date

January 2017

First Advisor

Amleh, Asma

Committee Member 1

Amleh, Asma

Committee Member 2

Shoeib, Tamer

Extent

48 p.

Document Type

Master's Thesis

Rights

The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy.

Institutional Review Board (IRB) Approval

Not necessary for this item

Comments

I am deeply grateful to my advisor Dr. Asma Amleh for her endless support, time, effort, and guidance. Furthermore, I acknowledge AUC for funding my laboratory research. I would also like to Acknowledge Mr. Mustafa Adel for his contributions to our project. Finally, I would like to Acknowledge Mr. Amged Ouf for his valuable advice and support.

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