Abstract

Cancer is one of the highest leading causes of death at the mean time. There are multiple approaches developed for cancer treatment including chemotherapy, radiation, and hormonal therapy. Due to the toxicity and inefficiency of such approaches, small molecules drugs (<0.5 kDa) have emerged to overcome the limitations of current therapeutics. The great potential of peptide drugs emerged from their targeted selectivity and rare resistance acquirement. Previous research has been carried on a 37 residue antimicrobial peptide, and showed dose dependent cytotoxicity on early stage Hepatocellular carcinoma cell line (HepG2). This 37-mer peptide was retrieved from the AUC Red Sea metagenomics data generated during AUC/KAUST Red Sea microbiome project and modified to enhance its anti-cancer activity. The current research aims at characterizing the cytotoxicity of the 37-mer peptide drug on an advanced stage of hepatocellular carcinoma cell line (SNU449). The anticancer effect of the peptide is tested on cancer cells proliferation, morphology, viability and migration. The peptide cytotoxic effect on normal human erythrocytes is tested, defining its hemolytic activity. Finally, we investigated the peptide antimicrobial property on gram-positive and gram-negative bacterial strains. Peptide treatment caused a dose dependent cytotoxicity on SNU449, affecting cellular morphology. The treatment caused differential expression in some major cancer hallmarks involved in proliferation, migration, apoptosis and autophagy. This suggests that upon treatment, cells undergo programmed cell death pathway. The molecular machinery involving apoptosis and autophagy are responsible for peptide cytotoxic effect on the cells. Peptide also showed no considerable hemolytic activity on human red blood cells upon application. Finally, the antimicrobial effect of the peptide is established on both gram positive and gram negative bacterial strains.

School

School of Sciences and Engineering

Department

Biotechnology Program

Degree Name

MS in Biotechnology

Graduation Date

9-9-2019

Submission Date

September 2019

First Advisor

Amleh, Asma

Committee Member 1

Mahmoud, Hamada Mohamed

Committee Member 2

Abdellatif, Ahmed

Extent

66 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. The author has granted the American University in Cairo or its agents a non-exclusive license to archive this thesis, dissertation, paper, or record of study, and to make it accessible, in whole or in part, in all forms of media, now or hereafter known.

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