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Benzyl Isothiocyanate As an Adjuvant Chemotherapy Option for Head and Neck Squamous Cell Carcinoma Mary Allison Wolf [email protected]

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Benzyl Isothiocyanate As an Adjuvant Chemotherapy Option for Head and Neck Squamous Cell Carcinoma Mary Allison Wolf Teter6@Marshall.Edu Marshall University Marshall Digital Scholar Theses, Dissertations and Capstones 2014 Benzyl Isothiocyanate as an Adjuvant Chemotherapy Option for Head and Neck Squamous Cell Carcinoma Mary Allison Wolf [email protected] Follow this and additional works at: http://mds.marshall.edu/etd Part of the Biological Phenomena, Cell Phenomena, and Immunity Commons, Medical Biochemistry Commons, Medical Cell Biology Commons, and the Oncology Commons Recommended Citation Wolf, Mary Allison, "Benzyl Isothiocyanate as an Adjuvant Chemotherapy Option for Head and Neck Squamous Cell Carcinoma" (2014). Theses, Dissertations and Capstones. Paper 801. This Dissertation is brought to you for free and open access by Marshall Digital Scholar. It has been accepted for inclusion in Theses, Dissertations and Capstones by an authorized administrator of Marshall Digital Scholar. For more information, please contact [email protected]. Benzyl Isothiocyanate as an Adjuvant Chemotherapy Option for Head and Neck Squamous Cell Carcinoma A dissertation submitted to the Graduate College of Marshall University In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences By Mary Allison Wolf Approved by Pier Paolo Claudio, M.D., Ph.D., Committee Chairperson Richard Egleton, Ph.D. W. Elaine Hardman, Ph.D. Jagan Valluri, Ph.D. Hongwei Yu, PhD Marshall University May 2014 DEDICATION “I sustain myself with the love of family”—Maya Angelou To my wonderful husband, loving parents, and beautiful daughter—thank you for everything you have given me. ii ACKNOWLEDGEMENTS First and foremost, I would like to thank my mentor Dr. Pier Paolo Claudio. He has instilled in me the skills necessary to become an independent and successful researcher. I will always be grateful for his guidance and support during each step of my studies and I value everything he has taught me over the years. I would also like to acknowledge the current and past lab members of the Claudio Lab: Dr. Flavia De Carlo, Miranda Carper, Sarah Mathis, Oksana Bailiff, Rounak Nande, Dr. Ilaria Naldi, Benji Pyles, and Colleen Conlon. Each of these individuals has contributed to my success in some way, and I am fortunate to have been given the opportunity to work alongside them. I would particularly like to recognize Dr. Flavia De Carlo and Miranda Carper for their guidance, input, and support throughout my time at Marshall. Their work ethic and drive have been truly inspirational to me and I cherish the lifelong friendship that has developed. I am also thankful for the members of McKown Translational Genomic Research Institute: Dr. Johannes Fahrmann, Dr. Sarah Miles, Ted Witte, Dr. Gabriella Ion, and Margaret McFarland. It has been a pleasure to work with such great individuals. I would especially like to recognize Dr. Johannes Fahrmann for all of his support. He was always available to help me troubleshoot problems and understand my data. He has a true passion for research and will make an amazing Principle Investigator. I am also appreciative of the guidance I received from Dr. Heath Damron. I would never have started down this path without him. His love for research is contagious, and I am thankful to have him as one of my first mentors. Dr. Anne Silvis has also been an excellent mentor. I appreciate all the advice and moral support she has provided with over the past few years. She is a great role model for me in both the research world and life. iii I am also truly grateful for my committee members: Dr. Richard Egleton, Dr. W. Elaine Hardman, Dr. Jagan Valluri, and Dr. Hongwei Yu. Their guidance and expertise have been instrumental to the success of my project. It has been a pleasure and honor to have them guide me through my research career at Marshall. Specials thanks to the Marshall University’s Biomedical Sciences program, especially Dr. Todd Green, Dr. Richard Niles, and Diane Maue. I am so fortunate to have had the opportunity to be a part of this program and I am appreciative of all the support and guidance I have been given since day one. Additional support came from the WV-NASA Space Grant Consortium. I am grateful that, at a time when funding for research continues to be cut, they supported my project. Many students in the state of WV would not be able to continue their studies without this funding. This journey has been anything but easy, and I constantly questioned if I had what it takes to complete the process. I would have thrown in the towel long ago if it had not been for my husband, Chris Wolf. He was my cheerleader and voice of reason, and constantly reminded me that there was a light at the end of the tunnel. Lastly, I would like to thank my daughter, Claire. Her arrival gave me the last bit of motivation I needed to finish this thesis. I want to instill in her the philosophy that you can accomplish anything you put your mind to. iv TABLE OF CONTENTS DEDICATION .......................................................................................................................................... ii ACKNOWLEDGEMENTS ..................................................................................................................... iii LIST OF TABLES ................................................................................................................................. viii LIST OF FIGURES ................................................................................................................................. ix LIST OF ABREVIATIONS .................................................................................................................... xi ABSTRACT ........................................................................................................................................... xiii Chapter 1 : Isothiocyanates Target Carcinogenesis during Tumor Initiation, Promotion, and Progression ...................................................................................................................................... 1 ABSTRACT .............................................................................................................................................. 2 INTRODUCTION .................................................................................................................................... 3 Mechanisms of Action .......................................................................................................................... 7 Uses in Cancer Therapy ...................................................................................................................... 11 Lung Cancer ........................................................................................................................................ 11 Breast Cancer ...................................................................................................................................... 12 Prostate Cancer ................................................................................................................................... 14 Pancreatic Cancer ................................................................................................................................ 15 Hematological Cancer ......................................................................................................................... 16 Head and Neck Cancer ........................................................................................................................ 17 Conclusions ......................................................................................................................................... 19 Chapter 2 : Head and Neck Squamous Cell Carcinoma ............................................................... 20 Epidemiology and Characterization .................................................................................................... 20 Classification and Staging ................................................................................................................... 22 Diagnosis and Treatment .................................................................................................................... 26 Pitfalls of Current Treatments ............................................................................................................. 29 Molecular Mechanisms of HNSCC .................................................................................................... 32 Models used to study HNSCC ............................................................................................................ 33 Chapter 3 : Benzyl Isothiocyanate Inhibits HNSCC Cell Migration and Invasion, and Sensitizes HNSCC Cells to Cisplatin. ........................................................................................................... 37 ABSTRACT ............................................................................................................................................ 38 INTRODUCTION .................................................................................................................................. 39 MATERIALS AND METHODS ............................................................................................................ 41 Materials ............................................................................................................................................. 41 v Cell Culture and Reagents..................................................................................................................
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