Protease Inhibitors as Cancer Chemopreventive Agents PDF
Preview Protease Inhibitors as Cancer Chemopreventive Agents
Protease Inhibitors as Cancer Chemopreventive Agents 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 Springer Science+Business Media, LLC Llbrary of Congress Cataloglng-ln-Publlcatlon Data Protease lnhlbitors as cancer chemopreventive agents I edited by Walter Troll, Ann R, Kennedy. p. cm. Inc I udes b 1b li ograph 1 ca I references and 1 ndex. ISBN 978-1-4613-6249-4 ISBN 978-1-4615-2882-1 (eBook) DOI 10.1007/978-1-4615-2882-1 1. Sancer--Chemoprevention. 2. Proteolytlc enzyme lnhlbltors -Therapeutic use. 1. Troll, Walter. II. Kennedy, Ann R. [DNLM, 1. Protease Inhibltors--therapeutic use. 2. Protease Inhlbitors--metabolism. 3. Neoplasms--preventlon & control. OU 138 P9885 1993J RC288.15.P77 1993 818.99·405--dc20 DNLM/DLC for Library of Congress 93-24959 CIP ISBN 978-1-4613-6249-4 © 1993 Springer Science+Business Media New York Originally published by Plenum Press New York in 1993 Softcover reprint of the hardcover 1s t edition 1993 AII rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Contributors Takaaki Aoyagi Institute of Microbial Chemistry, Shinagawa-ku, Tokyo 141, Japan Sila Banerjee Department of Obstetrics and Gynecology, New York Univer- sity Medical Center, New York, New York 10016 Anne H. Bates Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Albany, California 94710 Paul C. Billings Department of Radiation Oncology, University of Pennsyl- vania School of Medicine, Philadelphia, Pennsylvania 19104 Yehudith Birk Department of Biochemistry and Human Nutrition, Faculty of Agriculture, The Hebrew University of Jerusalem, Rehovot 76100, Israel Donald E. Bowman Departments of Biochemistry and Molecular Biology, School of Medicine, Indiana University, Indianapolis, Indiana 46202-5122 David L. Brandon Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Albany, California 94710 Ann F. Chambers The London Regional Cancer Centre, University of West- ern Ontario, London, Ontario, Canada N6A 4L6 Janice D. Chang Department of Biology, Massachusetts Institute of Tech- nology, Cambridge, Massachusetts 02139 Rita Colella Department of Biological Sciences, Rutgers University, Pis- cataway, New Jersey 08855. Present address: Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky 40292 v vi CONTRIBUTORS Pelayo Correa Department of Pathology, Louisiana State University Medical Center, New Orleans, Louisiana 70112 Lydia Cox Department of Environmental Medicine, New York University Medical Center, New York, New York 10016 Diane C. Currie Department of Environmental Medicine, New York Univer- sity Medical Center, New York, New York 10016 David T. Denhardt Department of Biological Sciences, Rutgers University, Piscataway, New Jersey 08855 Thomas H. Finlay Department of Obstetrics and Gynecology, New York University Medical Center, New York, New York 10016 Peter Flecker Institute for Physiological Chemistry, University of Mainz, W-6500 Mainz, Germany Elizabeth Fontham Department of Pathology, Louisiana State University Medical Center, New Orleans, Louisiana 70112 Krystyna Frenkel Departments of Environmental Medicine and Pathology, New York University Medical Center, New York, New York 10016 Mendel Friedman Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Albany, California 94710 Seymour J. Garte Department of Environmental Medicine, New York Uni- versity Medical Center, New York, New York 10016 Susan S. Kadner Department of Obstetrics and Gynecology, New York Uni- versity Medical Center, New York, New York 10016 Joseph Katz Department of Obstetrics and Gynecology, New York Univer- sity Medical Center, New York, New York 10016 Ann R. Kennedy Department of Radiation Oncology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 Mortimer Levitz Department of Obstetrics and Gynecology, New York Uni- versity Medical Center, New York, New York 10016 Daniel S. Longnecker Department of Pathology, Dartmouth Medical School, Hanover, New Hampshire 03755 Joan Motz Department of Environmental Medicine, New York University Medical Center, New York, New York 10016 Joseph Nickels, Jr. Department of Microbiology and Molecular Genetics, Rutgers University, New Brunswick, New Jersey 08903 CONTRIBUTORS vii Uma Raju Department of Obstetrics and Gynecology, New York University Medical Center, New York, New York 10016 George Ritchie Department of Physics, Rider College, Lawrenceville, New Jersey 08648 B. D. Roebuck Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755 Lorraine T. Schepis Department of Molecular Biology, Princeton University, Princeton, New Jersey 08530 Tomio Takeuchi Institute of Microbial Chemistry, Shinagawa-ku, Tokyo 141, Japan Snait Tamir Department of Obstetrics and Gynecology, New York University Medical Center, New York, New York 10016 Wataru Tanaka Institute of Microbial Chemistry, Shinagawa-ku, Tokyo 141, Japan Walter Troll Department of Environmental Medicine, New York University Medical Center, New York, New York 10016 Kazuo Umezawa Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Kohoku-ku, Yokohama 223, Japan Jonathan Yavelow Department of Biology, Rider College, Lawrenceville, New Jersey 08648 Preface Protease inhibitors (PIs) are widely distributed in plants and animals, and have a variety of functions, which include preventing digestion of seeds by insects and modifying blood clotting in animals. After it was noted that synthetic and natural inhibitors suppress two-stage carcinogenesis and breast cancer, extensive work investigating PIs as chemopreventive agents was started. PIs are unique in that they interfere with cancer development in a variety of ways, including suppression of oxygen radicals, oncogenes, and metastases. Epidemiologic evidence supports their prevention of major human cancers in populations that consume foods containing them. Their supervised use in humans is on the threshold of development. The epidemiologic discovery of the importance of lentils and other seeds rich in PIs in preventing many human cancers allowed us to look at the action of PIs as chemopreventive agents, as reviewed in Chapter I (Fontham and Correa). Chapter 2 (Kennedy) discusses the role of natural PIs (e.g., the Bowman-Birk inhibitor) as anticarcinogens and the possible limitations of their use. In Chapter 3 (Kennedy), the transformation of C3HI lOTlh cells caused by carcinogens and promoters is shown to be suppressed by PIs. Bowman (Chapter 4) relates the discovery of inhibitors in soybeans that are distinct from the Kunitz inhibitor, and the occurrence of a similar inhibitor in peanuts and other legumes. Chapter 5 (Birk) is an overview of PIs of plant origin and their role in human nutrition. In Chapter 6, Brandon and colleagues report on the measurement of soybean trypsin inhibitors by monoclonal antibodies, their possible use for cellular delivery, and the effect of food processing on the survival of the inhibitors. Chapter 7 (Um ezawa et at.) concerns low-molecular-weight inhibitors, isolated from strep tomycetes, that have been shown to suppress cancer in animal and some human experiments and are also useful for in vitro and oncogene expression studies. PI synthesis by MCF-7 breast cancer cell lines is discussed in Chapter 8 (Finlay et al.). ai-Trypsin and chymotrypsin inhibitors synthesized by breast cancers may inhibit metastasis. In Chapter 9, Flecker analyzes the structure-activity relation- ix x PREFACE ships of the Bowman-Birk inhibitor of serine proteinases, with a view toward the design of new cancer chemopreventive agents. Troll (Chapter 10) discusses the prevention of cancer by vitamin B3 compounds, PIs that are available for human use. Billings (Chapter 11) details approaches to studying the target en zymes of anticarcinogenic PIs. In Chapter 12, Colella and colleagues document the anticarcinogenic activities of naturally occurring cysteine proteinase inhibi tors. These PIs prevent metastasis of tumors and are distinct from serine PIs. Yavelow and colleagues (Chapter 13) identify a chymotrypsin cell membrane enzyme that acts as a possible receptor for chymotrypsin inhibitors. Frenkel (Chapter 14) describes the role of reactive oxygen species in biological damage and the effect of some chemopreventive agents. Chapters 15 (Garte et al.) and 16 (Chang and Kennedy) discuss PI suppression of the actions induced by the ras and c-myc oncogene, respectively. Chapter 17 (Levitz et al. ) reviews the role of esterases in steroid hormone turnover. Esterases in breast cyst fluid hydrolyze steroid esters, modifying their action. The action of PIs in inducing pancreatic cancer in animal models is reviewed by Roebuck and Longnecker (Chapter 18). Contents Chapter 1 The Epidemiologic Approach to the Study of Protease Inhibitors Elizabeth Fontham and Pelayo Correa 1. Introduction ............................................. . 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 ........................................ 15 2.1. Effects of Protease Inhibitors on Growth .................. 15 2.2. Effects of Protease Inhibitors on the Pancreas· . . . . . . . . . . . . . . 16 2.3. Potential Effects of Protease Inhibitors on the Immune System ...................................... 22 3. The Soybean-Derived BBI as an Anticarcinogenic Agent. . . . . . . . . 23 3.1. Review of Data on the Anticarcinogenic Activity of BBI . . . . . 23 xi xii CONTENTS 3.2. Limitations of BBI as a Human Cancer Chemopreventive Agent............................................... 44 4. Mechanism of Action of the Anticarcinogenic Protease Inhibitors ........................................ 50 5. Summary ................................................ 54 6. References ............................................... 55 Chapter 3 In Vitro Studies of Anticarcinogenic Protease Inhibitors. . . . . . . . . . . . . 65 Ann R. Kennedy 1. Introduction .............................................. 65 2. Mechanism of Action of the Anticarcinogenic Protease Inhibitors in the Suppression of Transformation in Vitro .................... 80 3. References ............................................... 86 Chapter 4 Discovery and Background of the Bowman-Birk Protease Inhibitors ........................................... 93 Donald E. Bowman 1. Origin of Interest in Legumes ............................... 93 2. Unexpected Protease Inhibition by Amylase Inhibition Preparations ..................................... 93 3. References............................................... 95 Chapter 5 Protease Inhibitors of Plant Origin and Role of Protease Inhibitors in Human Nutrition: Overview ................................... 97 Yehudith Birk 1. Introduction 97 2. Protease Inhibitors from Legume Seeds ...................... . 98 2.1. STI ................................................ . 98 2.2. BBI ............................................... . 98 3. Protease Inhibitors from Other Plant Sources .................. . 101 3.1. Potato Protease Inhibitors ............................. . 101 3.2. Squash Protease Inhibitors ............................. . 101 3.3. Protease Inhibitors in Cereals .......................... . 101 4. Role in Nutrition ......................................... . 102 4.1. Effect on Growth .................................... . 102 4.2. Effects on the Pancreas ............................... . 102
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