Author

Nouran Adly

Abstract

Hepatocellular carcinoma (HCC) has been a major health problem in Egypt with extensive efforts and studies done in enhancing chemotherapeutic drugs for more optimal results. Existing chemotherapeutic drugs are costly with problematic side effects. Recent studies have demonstrated the anticancer potential of antihistamines on different types of cancer, including HCC. Antihistamines have been proven to induce cell cycle arrest and/or apoptosis through different mechanisms depending on their role on different cancer types. The second generation antihistamine, loratadine (LOR), was found to have tumor inhibiting effects on human colon carcinoma cell line. However, no studies were done neither on the influence of loratadine on HCC cells, nor the effect of the combination of loratadine with existing chemotherapeutic drugs to test its potential to improve chemotherapy. Here, the cytotoxic potential of loratadine and the combination of loratadine and cisplatin on HepG2 and SNU449 were investigated. Cell viability assay was performed to show that there is a dose-dependent cytotoxic effect of LOR on both HCC cell lines and that there is a synergistic to additive effects when LOR was introduced to the cells in combination with cisplatin when the IC50 of both drugs were used. Loratadine did not show a cytotoxic effect on normal cells when used in low concentrations (<55.6 µM). However, when used in higher concentration (<73.2 µM), LOR showed a high cytotoxic effect. Apoptotic and cell cycle analysis showed that loratadine induced apoptosis and cell cycle arrest in the G2/M phase in SNU449 cells, while combination of loratadine and cisplatin may induce necrosis and cell cycle arrest in G2/M phase. Taken together, loratadine offers a strong basis to be further developed either alone or in combination with cisplatin as a treatment option for advanced hepatocellular carcinoma. Further studies are required to test the effect of loratadine treatment in vivo and perhaps to test the effect of loratadine in combination with sorafenib in vitro and in vivo for the hope to improve HCC therapy.

Department

Biotechnology Program

Degree Name

MS in Biotechnology

Date of Award

2-1-2018

Online Submission Date

September 2017

First Advisor

Zada, Suher

Committee Member 1

Abdellatif, Ahmed

Committee Member 2

Khalifa, Amani

Document Type

Thesis

Extent

64 p.

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.

IRB

Not necessary for this item

Comments

I would like to thank my mother, Gihan Sayed, and my father, Alaa Adly, who helped me tremendously during this journey, for their emotional support, for taking care of my daughter and for helping me through my pregnancies. I would also like to thank my husband, Fadi Sharaf, for his emotional and nancial support and for being so patient with me those 2 years. I would like to thank my sister, Alia Adly, for helping me edit this thesis, using LaTex (www.latex- project.org). Also, I would like to thank my daughter, Joanna, for her patience and would like to apologize for all the days and nights I was too busy to be beside her. I would like to express my gratitude to my supervisor and advisor: Dr. Suher Zada, for her support and guidance. She encouraged me and believed in me all throughout the thesis. I would like to express my deep appreciation and gratitude to Dr. Eman Elahwany, for her great advice and for helping me construct my thesis and helping me decide which antihistamine to work with. I would like to extend many thanks to Noha Nagdy for being always available when I need her, for her kind words whenever I am panicking and for her scienti c advice whenever I take her opinion in anything concerning my thesis. Eman Abdulghany for welcoming me to the team and helping me a lot in designing my MTTs and sharing her knowledge and experience with me. I would like to thank all the professors who taught me in the Biotechnology program: Dr. Asma Amleh, Dr. Hamza Eldorry, Dr, Ahmed Ehab, Dr. Andreas Kakarougkas, Dr. Hassan Azzazy, Dr. Walid Fouad, Dr. Ramy Aziz, and Dr. Ahmed Moustafa. I would like to express my appreciation to Amged Ouf, as he always provided help and explained many scienti c concepts that were missing in the beginning of my journey. I was also very fortunate for the opportunity to get to know such brilliant, kind, sweet, helpful colleagues and friends throughout the 2 years. My gratitude to Menna Ghouraba for her continuous support, whether personally or scienti cally, she quickly transformed to be a very dear person to me. I would like to thank Noha Motaz, Amani Abdel-Motaleb , Nancy Hassanein, Salma El Shafei, Mona Elradi, Myret Ghabriel, Razan Jamil, Amira Atwa, Nada Elzahed, Menna Elfar, Noha Saad, Jasmine Omran, and Ahmed Samir for all their help and support. I would like to send my appreciation to my friends in KSA: Miada Ahmed, who helped me edit my proposals, and Muneira El Harby (May she rest in peace), for taking care of my daughter while I was working on my studies. Finally I would like to thank the AUC for providing research grant which funded this project and for Laboratory fellowship for partially funding my studies.

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