Protease Inhibitors as Cancer Chemopreventive Agents

Transcription

1 C" Protease Inhibitors as Cancer Chemopreventive Agents Edited by Walter Troll New York University Medical Center New York, New York and Ann R. Kennedy University of Pennsylvania School of Medicine Philadelphia, Pennsylvania Plenum Press New York and London

2 Contents Chapter 1 The Epidemiologic Approach to the Study of Protease Inhibitors 1 Elizabeth Fontham and Pelayo Correa 1. Introduction 1 2. Descriptive Epidemiology 1 3. Analytical Epidemiology 2 4. Tools Needed for Epidemiologic Studies 4 5. Intervention Studies 5 6. Cancer Prevention 6 7. Epilogue 6 8. References 7 Chapter 2 Anticarcinogenic Activity of Protease Inhibitors: Overview 9 Ann R. Kennedy 1. Review of Data Showing Anticarcinogenic Activity of Protease Inhibitors 9 2. Potential Adverse Effects of Anticarcinogenic Protease Inhibitors Effects of Protease Inhibitors on Growth Effects of Protease Inhibitors on the Pancreas Potential Effects of Protease Inhibitors on the Immune System The Soybean-Derived BBI as an Anticarcinogenic Agent Review of Data on the Anticarcinogenic Activity of BBI 23

3 xii CONTENTS 3.2. Limitations of BBI as a Human Cancer Chemopreventive Agent Mechanism of Action of the Anticarcinogenic Protease Inhibitors Summary References 55 Chapter 3 In Vitro Studies of Anticarcinogenic Protease Inhibitors 65 Ann R. Kennedy 1. Introduction Mechanism of Action of the Anticarcinogenic Protease Inhibitors in the Suppression of Transformation in Vitro References 86 Chapter 4 Discovery and Background of the Bowman-Birk Protease Inhibitors 93 Donald E. Bowman 1. Origin of Interest in Legumes Unexpected Protease Inhibition by Amylase Inhibition Preparations References 95 Chapter 5 Protease Inhibitors of Plant Origin and Role of Protease Inhibitors in Human Nutrition: Overview 97 Yehudith Birk 1. Introduction Protease Inhibitors from Legume Seeds STI BBI Protease Inhibitors from Other Plant Sources Potato Protease Inhibitors Squash Protease Inhibitors Protease Inhibitors in Cereals Role in Nutrition Effect on Growth Effects on the Pancreas 102

4 CONTENTS xiii 5. Therapeutic Potential of Protease Inhibitors References 104 Chapter 6- Antigenicity of Soybean Protease Inhibitors 107 David L. Brandon, Anne H. Bates, and Mendel Friedman 1. Introduction Kunitz Trypsin Inhibitor Immunochemistry of KTI Specificities of Monoclonal Antibodies to KTI Immunochemistry of the Bowman-Birk Inhibitor Sources and Treatment of Protease Inhibitors Polyclonal Antibodies Monoclonal Antibodies to BBI Relationship of Inhibitory Activities and Antigenicity Immunoassays of KTI and BBI Antibody Titrations, Inhibition ELISA, and Competition ELISA Sandwich ELISA Availability of Cell Lines Examples of Use of Monoclonal Antibodies to Analyze Soy Foods and Germ Plasm Autoclaved Soy Meal Infant Formula Immunoaffinity Methods Screening the Genus Glycine Other Effects of Food Processing on Antigenicity of KTI Chemical Changes during Food Processing Effects of Alkali Effects of Carbohydrates Conclusions References 126 Chapter 7 Low-Molecular-Weight Protease Inhibitors of Microbial Origin 131 Kazuo Umezawa, Takaaki Aoyagi, Wataru Tanaka, and Tomio Takeuchi 1. Introduction Endopeptidase Inhibitors Exopeptidase Inhibitors References 138

5 xiv CONTENTS Chapter 8 Protease Inhibitor Synthesis by MCF-7 Breast Cancer Cells 141 Thomas H. Finlay, Susan S. Kadner, and Snait Tamir 1. Introduction and Scope of the Chapter a,-at and a,-achy Function and Properties Site of Synthesis Regulation of Synthesis a,-at and a,-achy in MCF-7 Cells MCF-7 Breast Cancer Cell Line Synthesis of a,-at and a,-achy by MCF-7 Cells Kinetics of a r AT and a,-achy Synthesis and Secretion Stimulation of a,-at and a,-achy Synthesis by Steroid Hormones, Inflammatory Mediators, and Growth Factors Production of a r AT and a,-achy by Various MCF-7 Sublines Perspectives and Conclusions References 154 Chapter 9 Analysis of Structure-Activity Relationships of the Bowman Birk Inhibitor of Serine Proteinases: Toward a Rational Design of New Cancer Chemopreventive Agents 161 Peter Flecker 1. Introduction Biological Aspects Prospects of Protein Engineering for the Design of Anticarcinogenic Agents A New Approach to BBI-Type Proteinase Inhibitors by Synthetic Gene Technology Trypsin-Sepharose as a Matrix with Complementary Structure Is Required for Refolding of Proteinase Inhibitor Variants BBI Has Structural Similarity to the COOH-Terminal Part of the B Chain of Laminin Conclusions References 174

6 CONTENTS xv Chapter 10 Prevention of Cancer by Vitamin B 3 (Nicotinamide and Nicotinic Acid): A Protease Inhibitor Available in Pure Form 177 Walter Troll 1. Introduction Dietary Pis Suppress Cancer Interference with Oxyradical Formation Suppression of Transformation-Caused Oncogene Transfection Suppression of Carcinogenesis Suppression of Two-Stage Carcinogenesis by Applying Pis to Mouse Skin Suppression of Two-Stage Carcinogenesis and Breast Cancer in Rodents by Feeding Soybean Diets Suppression of Tumor Promotion in Mice by Feeding NA- Supplemented Diets Mechanism of Cancer Prevention by Feeding Pis Concluding Remarks References 187 Chapter 11 Approaches to Studying the Target Enzymes of Anticarcinogenic Protease Inhibitors 191 Paul C. Billings 1. Introduction Results and Discussion Defined Substrates as Tools to Identify Proteolytic Activities Which Are Inhibited by the Anticarcinogenic Protease Inhibitors The Use of Affinity Chromatography to Identify Proteins Which Specifically Interact with Anticarcinogenic Protease Inhibitors References 197 Chapter 12 Anticarcinogenic Activities of Naturally Occurring Cysteine Proteinase Inhibitors 199 Rita Colella, Ann F. Chambers, and David T. Denhardt 1. Introduction Cysteine Proteinases 200

7 xvi CONTENTS 3. The Cystatin Superfamily Mode of Inhibition Cystatins and Metastasis References 211 Chapter 13 Cell Membrane Enzymes Containing Chymotrypsin-like Activity 217 Jonathan Yavelow, Lorraine T. Schepis, Joseph Nickels, Jr., and George Ritchie 1. Introduction Effect of Chymotrypsin Inhibitors on in Vitro Cell Transformation Properties of Cell Membrane Enzymes Containing Chymotrypsinlike Activity Potential Cellular Substrates for Membrane Chymotrypsin-like Enzymes Fluorescence Anisotropy as a Tool for Studying the Anticarcinogenic Action of Chymostatin Conclusions References 223 Chapter 14 The Role of Reactive Oxygen Species in Biological Damage and the Effect of Some Chemopreventive Agents 227 Krystyna Frenkel 1. Formation of Reactive Oxygen Species Formation of H 2 O 2 and Oxidized DNA Bases By Tumor Promoter-Stimulated PMNs By Hepatic Microsomes Inhibition of H 2 O 2 Formation by Stimulated PMNs Inhibition by Protease Inhibitors Inhibition by Sarcophytol A References 243 Chapter 15 Protease Inhibitor Suppression of ras Oncogene-Induced Transformation 251 Seymour J. Garte, Lydia Cox, Diane C. Currie, Joan Motz, and Walter Troll 1. Introduction Methods Cell Culture and DNA Isolation 253

8 CONTENTS xvii 2.2. DNA-Mediated Transfection Characterization of Transformed Phenotype Southern Blot Hybridization Northern Blot Hybridization Results Dose Response of Protease Inhibitors on ras Transformation Effects on aph Gene Transfection Time Course Studies Influence of Cell Proliferation Subculture and Serum Conditions Reversibility ras Gene Expression Retinoic Acid Effects Discussion References 261 Chapter 16 Suppression of c-myc by Anticarcinogenic Protease Inhibitors 265 Janice D. Chang and Ann R. Kennedy 1. Introduction The Oncogene c-myc and Malignant Transformation Activation of c-myc Function of the Normal c-myc Gene Mechanism of c-myc Regulation c-myc Expression Is Reduced in Protease Inhibitor-Treated Proliferating Mouse Fibroblasts Cells Progress through the Cell Cycle in the Absence of an Increase in c-myc RNA Levels Antipain Increases the Half-Life of the c-myc Message Possible Mechanisms by Which Protease Inhibitors Regulate c-myc Expression, Concluding Remarks References 277 Chapter 17 A Role for Esterases in Steroid Hormone Turnover 281 Mortimer Levitz, Sila Banerjee, Joseph Katz, Uma Raju, and Thomas H. Finlay 1. Introduction and Scope of the Chapter Endogenous Steroid Esters 282

9 xviii CONTENTS 2.1. Steroid Esters in Body Fluids Steroid Esters in Tissues Steroid Fatty Acid Ester Production in Vitro Steroid Ester Metabolism: Physiological Implications In Man In MCF-7 Cells Esterification and Deesterification Enzymes Transesterification Breast Cyst Fluid Esterase Perspectives and Conclusions References 292 Chapter 18 Protease Inhibitors and Pancreatic Carcinogenesis 295 B. D. Roebuck and Daniel S. Longnecker 1. Pancreatic Cancer Human Disease Animal Models of Pancreatic Cancer Cholecystokinin Hypothesis Response of the Pancreas to Trypsin Inhibitors Soybean Products Camostate (FOY-305) Carcinogenesis and Cholecystokinin Rat Pancreas Other Species Including Humans Conclusion References 301 Index 305