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Evaluation of Antibreast and Antiprostate Cancer Activities EVALUATION OF ANTIBREAST AND ANTIPROSTATE CANCER ACTIVITIES OF SELECTED MEDICINAL PLANTS FROM SOME PARTS OF KENYA MISONGE JARED ONYANCHA P97/24524/2011 A THESIS SUBMITTED IN FULFILLMENT OF THE REQUIREMENTS FOR THE AWARD OF THE DEGREE OF DOCTOR OF PHILOSOPHY (PHARMACOGNOSY AND COMPLEMENTARY MEDICINE) IN THE SCHOOL OF PHARMACY OF KENYATTA UNIVERSITY NOVEMBER, 2019 ii DECLARATION This thesis is my original work and has not been presented for a degree in any other University or any other award. Jared Misonge Onyancha (Reg. No. P97/24524/2011) Signature ________________________________Date_____________ School of Pharmacy, Kenyatta University SUPERVISORS We confirm that the work reported in this thesis was carried out by the student under our supervision. Prof. Nicholas Kamindu Gikonyo Signature __________________________Date_____________ School of Pharmacy Prof. Michael Muita Gicheru Signature ___________________________Date____________ School of Pure and Applied Sciences Dr. Sabina Wangui Wachira Signature ___________________________Date____________ Centre for Traditional Medicine and Drug Research, Kenya Medical Research Institute iii DEDICATION This work is dedicated to my family, Eucabeth Bosibori (wife), sons: Enosh Osano, David Onyancha and daughters: Tabitha Moke, Ruth Moraa and Esther Kemunto. iv ACKNOWLEDGEMENTS I am grateful to God, creator of the Universe. He bestowed upon me the courage and determination to carry out this research. Secondly, I owe deep gratitudes to my supervisors Prof. Nicholas Gikonyo, Prof. Michael Gicheru both of Kenyatta University and Dr. Sabina Wachira of Kenya Medical Research Institute (KEMRI) for their timely guidance. I recognise the Kenya Medical Research Institute for the opportunity to carry out anticancer and toxicity studies. Mr. Gervson Moriasi (Mount Kenya University) and Mr. Gilbert Mukindia (Kenyatta University) are also appreciated for their technical support. Tribute goes to the school of post graduate studies of Kenyatta University, for granting me an opportunity to undertake PhD studies. Other people who can’t be left out in this acknowledgement are Dr. Mary Akinyi of Kenya Methodist University and Dr. Gladys Mokua of Kenyatta University for their assistance and willingness to provide assistance on spectral analysis. Least but not last, I express my gratitude to my family members and friends who went out of their way to fund this work in little or big way, I am obliged and thankful to my mother Biliah Kemuma, my father Peter Onyancha, sisters Annet Kwamboka and Sarah Kerubo, My Brother Stephen Karani and relatives for their highly valuable contributions, patience, moral support and prayers. All those, who were a constant source of inspiration and encouragement throughout my studies, collegues and friends who sponsored this work at the time of need are highly appreciated. v TABLE OF CONTENTS DECLARATION ........................................................................................................ ii DEDICATION ........................................................................................................... iii LIST OF TABLES ................................................................................................... xii LIST OF PLATES .................................................................................................. xiv LIST OF FIGURES ................................................................................................. xv LIST OF SCHEMES .............................................................................................. xvi LIST OF APPENDICES ....................................................................................... xvii ABBREVIATIONS AND ACRONYMS .............................................................. xxii ABSTRACT ............................................................................................................ xxv CHAPTER ONE: INTRODUCTION ...................................................................... 1 1.1 Background information ..................................................................................... 1 1.2 Problem statement .............................................................................................. 2 1.3 Justification ........................................................................................................ 3 1.4 Research questions ............................................................................................. 4 1.5 Hypothesis .......................................................................................................... 5 1.6 Objectives ........................................................................................................... 5 1.6.1 General objective ......................................................................................... 5 1.7 Study significance and outputs ........................................................................... 6 CHAPTER TWO: LITERATURE REVIEW ......................................................... 7 2.1 The biology and pathophysiology of cancer ...................................................... 7 2.2 Aetiology of cancer ............................................................................................ 8 2.2.1 Physical carcinogens .................................................................................... 8 2.2.2 Chemical carcinogens .................................................................................. 9 vi 2.2.3 Biological carcinogens ................................................................................. 9 2.2.4 Diet, inactivity and obesity ........................................................................ 10 2.4.5 Hereditary .................................................................................................. 11 2.4.6 Hormones ................................................................................................... 12 2.4.7 Autoimmune diseases ................................................................................ 13 2.5 Staging systems for cancers.............................................................................. 13 2.6 Classification of cancers ................................................................................... 15 2.6.1 Carcinomas ................................................................................................ 15 2.6.2 Sarcomas .................................................................................................... 16 2.6.3 Leukemia, lymphoma and multiple myeloma ........................................... 16 2.6.4 Melanoma .................................................................................................. 17 2.7 The burden of cancer (incidences and mortality) ............................................. 18 2.7.3 Cervical cancer .......................................................................................... 21 2.8 Management of cancer ..................................................................................... 21 2.8.1 Radiotherapy .............................................................................................. 22 2.8.2 Surgery ....................................................................................................... 22 2.8.3 Chemotherapy ............................................................................................ 22 2.8.4 Hormonal therapy ...................................................................................... 25 2.8.5 Immunotherapy .......................................................................................... 26 2.8.6 Laser therapy.............................................................................................. 27 2.8.7 Palliative care ............................................................................................. 28 2.8.8 Photodynamic therapy (PDT) .................................................................... 29 2.8.9 Targeted therapy ........................................................................................ 30 2.8.10 Complementary and alternative medicine ............................................... 30 vii 2.9 Anticancer drugs of natural origin .................................................................... 31 2.10 Classes of phytochemicals used for management of cancer .......................... 31 2.11 Screening of plants for discovery of anticancer drugs ................................... 33 2.12 Selection of plants for screening anticancer activities ................................... 34 2.12.1 Random screening approach .................................................................... 34 2.12.2 Ethnopharmacological approach.............................................................. 35 2.12.3 Chemosystematic approach ..................................................................... 36 2.12.4 Ecological approach ................................................................................. 37 2.12.5 Computational approach .......................................................................... 39 2.13 Bioassay techniques for anticancer activities ................................................. 40 2.13.1 Tetrazolium reduction assays................................................................... 42 2.13.2 Resazurin reduction assay ........................................................................ 42 2.13.3 Sulforhodamine B (SRB) assay ............................................................... 43 2.13.4
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