PLANTS THAT FIGHT CANCER Also available from CRC Press: Bioactive Compounds from Natural Sources Edited by Corrado Tringali ISBN 0-7484-0890-8 (hardback) Biochemical Targets of Plant Bioactive Compounds A pharmacological reference guide to sites of action and biological effects Gideon Polya ISBN 0-415-30829-I (hardback) Phytochemical Dictionary (Second Edition) A handbook of bioactive compounds from plants Edited by Jefery B. Harborne, Herbert Baxter and Gerard Moss ISBN 0-7484-0620-4 (hardback) Taxus The genus Taxus Edited by Hideji Itokawa and Kuo-Hsiung Lee ISBN 0-415-29837-7 (hardback) Mistletoe The genus Viscum Edited by Arndt Bussing ISBN 90-5823-092-9 (hardback) Hypericum The genus Hypericum Edited by Edzard Ernst ISBN 0-415-36954-I (hardback) Oregano The genera Origanum and Lippia Edited by Spiridon E. Kintzios ISBN 0-415-36943-6 (hardback) Sage The genius Salvia Edited by Spiridon E. Kintzios ISBN 90-5823-005-8 (hardback) Sho-Saiko-To Scientific evaluation and clinical applications Edited by Yukio Ogihora and Mosaki Aburada ISBN 0-415-30837-2 (hardback) PLANTS THAT FIGHT CANCER Edited by Spiridon E. Kintzios and Maria G. Barberaki CRC PRESS Boca Raton London New York Washington, D.C. TF1582 disclaimer.fm Page 1 Wednesday, December 10, 2003 10:24 AM Library of Congress Cataloging-in-Publication Data Plants that Þght cancer / edited by Spiridon E. Kintzios and Maria G. Barberaki. p. ; cm. Includes bibliographical references and index. ISBN 0-415-29853-9 (hardback: alk. paper) 1. Herbs—Therapeutic use. 2. Cancer—Treatment. 3. Medicinal plants. 4. Materia medica, Vegetable. 5. Pharmacognosy. [DNLM: I. Neoplasms—drug therapy. 2. Phytotherapy. 3. Plant Extracts—therapeutic use. QZ 267 P714 2003] I. Kintzios, Spiridon E. II. Barberaki, Maria G. RC271.H47 P56 2003 616.99'4061—dc21 2003005700 This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microÞlming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher. All rights reserved. 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Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identiÞcation and explanation, without intent to infringe. Visit the CRC Press Web site at www.crcpress.com © 2004 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 0-415-29853-9 Library of Congress Card Number 2003005700 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0 Printed on acid-free paper Eleni Grafakou, Vaggelis Kintzios and all people giving their personal fight against cancer Contents List of contributors ix Preface x 1 What do we know about cancer and its therapy? 1 1. A brief overview of the disease and its treatment 1 1.1. Incidence and causes 1 1.2. Classification of cancer types 3 1.3. Therapy 4 1.3.1. Conventional cancer treatments 4 1.3.2. Advanced cancer treatments 6 1.3.3. Other advanced therapies 9 1.3.4. Alternative cancer treatments 9 1.4. From source to patient: testing the efficiency of a candidate anticancer drug 10 1.4.1. Preclinical tests 10 1.4.2. Phases of clinical trials 13 1.4.3. Clinical trial protocols 13 2 Plants and cancer 15 2. The plant kingdom: nature’s pharmacy for cancer treatment 15 2.1. Brief overview of the general organization of the plant cell 15 2.2. The chemical constituents of the plant cell 16 2.2.1. Primary metabolites 16 2.2.2. Secondary metabolites 17 2.3. Why do plant compounds have an anticancer activity? 17 2.4. Chemical groups of natural products with anticancer properties 19 2.5. Biotechnology and the supply issue 32 3 Terrestrial plant species with anticancer activity: a presentation 35 3.1. Introduction: general botanical issues 35 3.2. Species-specific information 36 3.2.1. The guardian angels: plant species used in contemporary clinical cancer treatment 36 viii Contents 3.2.2. Promising candidates for the future: plant species with a laboratory-proven potential 72 3.2.3. The fable: where tradition fails to meet reality 160 3.2.4. Other species with documented anticancer activity 166 4 Cytotoxic metabolites from marine algae 195 4.1. Cytotoxic metabolites from marine algae 195 4.2. Cytotoxic metabolites from chlorophyta 198 4.3. Cytotoxic metabolites from rhodophyta 211 4.4. Cytotoxic metabolites from phaeophyta 221 4.5. Cytotoxic metabolites from microalgae 227 Conclusions 240 Appendix: chemical structures of selected compounds 242 References 274 Index 289 Contributors Spiridon E. Kintzios Vassilios Roussis Agricultural University of Athens University of Athens Faculty of Agricultural Biotechnology School of Pharmacy Laboratory of Plant Physiology Department of Pharmacognosy and Iera Odos 75, Athens, Greece Chemistry of Natural Products Tel. ϩ3-010-5294292 Panepistimiopolis Zografou E-mail: [email protected] Athens 157 71, Greece Tel. ϩ3-010-7274592 Maria G. Barberaki E-mail: [email protected] Agricultural University of Athens Faculty of Agricultural Biotechnology Costas Vagias Laboratory of Plant Physiology University of Athens Iera Odos 75, Athens, Greece School of Pharmacy Tel. ϩ3-010-5294292 Department of Pharmacognosy and E-mail: [email protected] Chemistry of Natural Products Panepistimiopolis Zografou Olga G. Makri Athens 157 71, Greece Agricultural University of Athens Faculty of Agricultural Biotechnology Leto – A. Tziveleka Laboratory of Plant Physiology University of Athens Iera Odos 75, Athens, Greece School of Pharmacy Tel. ϩ3-010-5294292 Department of Pharmacognosy and E-mail: [email protected] Chemistry of Natural Products Panepistimiopolis Zografou Theodoros Matakiadis Athens 157 71, Greece Agricultural University of Athens Faculty of Agricultural Biotechnology Laboratory of Plant Physiology Iera Odos 75, Athens, Greece Tel. ϩ3-010-5294292 E-mail: [email protected] Preface This is a book about the most fearsome disease of modern times, which will strike every fourth citizen of a developed country sometime during his life: cancer. It is not a book about the pre- vention of cancer, but rather its treatment with plant-derived chemicals. It is an up-to-date and extensive review of plant genera and species with antitumor and antileukemic properties that have been documented in a strictly scientific sense. From the layman to the medical expert, the book is addressed to people seeking information on novel opportunities on disease therapy in order to make decisions about care programs. Purpose-wise, the book is written in colloquial style. The volume comprises four chapters. In the first chapter, the current knowledge of the nature of cancer and the main types of the disease are briefly described. In the second chapter, the various approaches for treating cancer – including conventional, advanced and alternative methods – are presented, while a relative emphasis is given on the chemotherapy of cancer. The restrictions and risks of each approach are comparatively reviewed. The second chapter of the book is a general review of plant-derived groups of compounds with anticancer properties, including their chem- istry, biosynthesis and mode of action. Evolutionary aspects of the anticancer properties of plants are presented and a separate chapter is devoted on the application of biotechnology in this field. The third, most extensive chapter of the book contains detailed information on each of more than 150 anticancer terrestrial plant genera and species. Topics include tradition and myth, dis- tribution, botany, culture, active ingredients and product application (including an analysis of expected results and risks) along with photographs and illustrations of each species. In addition, further information can be found on plant species with equivocal or minor anticancer value. Although the traditional sources of secondary metabolites were terrestrial higher plants, animals and microorganisms, marine organisms have been the major targets for natural products research in the past decade. In the fourth chapter of the book, algal extracts and isolated metabolites hav- ing cytotoxic and antineoplastic activity and with the potential for pharmaceutical exploitation are reviewed, along with the phylogeny and physiology of the organisms. Emphasis is given to the chemical