Table Of ContentBiodiversity, Natural Products
and Cancer Treatment
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Biodiversity, Natural Products
and Cancer Treatment
Edited by
Victor Kuete (University of Dschang, Cameroon)
Thomas Efferth (University Mainz, Germany)
World Scientific
NEW JERSEY • LONDON • SINGAPORE • BEIJING • SHANGHAI • HONG KONG • TAIPEI • CHENNAI
9085_9789814583503_TP.indd 2 13/6/14 11:31 am
Published by
World Scientific Publishing Co. Pte. Ltd.
5 Toh Tuck Link, Singapore 596224
USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601
UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE
Library of Congress Cataloging-in-Publication Data
Biodiversity, natural products and cancer treatment / [edited by] Victor Kuete, Thomas Efferth.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-9814583503 (hardcover : alk. paper) -- ISBN 9814583502 (hardcover : alk. paper)
I. Kuete, Victor, editor. II. Efferth, Thomas, 1960– editor.
[DNLM: 1. Neoplasms--drug therapy. 2. Biodiversity. 3. Biological Products--therapeutic use.
4. Ethnopharmacology--methods. 5. Materia Medica--therapeutic use. 6. Phytotherapy--methods.
QZ 267]
RC262
616.99'4061--dc23
2014018400
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
The cover image shows a frog of the genus Laptodactylus sitting in a Clusia blossom. Clusia species
produce antibacterial compounds, some of which are also cytotoxic towards cancer cells. The tissue
in the background represents a colon carcinoma immunohistochemically stained for the proliferation
marker Ki-67.
Copyright © 2014 by World Scientific Publishing Co. Pte. Ltd.
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Preface
Majoradvancesinmodernmedicineandpharmacologyweremadepossi-
ble by the presence of chemical structures in nature, i.e. molecules that
have developed during millennia of evolution of life in terrestrial and
marine microorganisms, plants and animals. The majority of clinically
established anticancer drugs are either natural products, derivatives of
them, or molecules that are based on mechanistic principles taken from
nature.Thisseeminglyunexpectedhighnumberofmoleculesfromnature
in cancer therapy is not peculiar to the field of oncology. In medicine in
general,aconsiderableproportionofalldrugsacrossallthedifferentther-
apeuticfieldshavetheiroriginsinnaturalcompounds.
Bearinginmindthattheveryfirstchemicalusedfortherapeuticpur-
poseswasmorphineisolatedfromPapaversomniferumin1804bytheGer-
manpharmacistFriedrichWilhelmAdamSertürmer,itshouldberealized
that modern pharmacotherapy is not much older than two centuries. On
the other hand, the various traditional medicines all around the world
are probably as old as mankind. While the elaborate forms of traditional
medicines such as traditional Chinese medicine,Ayurveda and others are
well documented with century- or millennia-old written documents still
accessible,othertraditionalformsofmedicinearehandeddownfromgen-
erationtogenerationbyoraltradition,thuslosingtheirveryfirstrootswith
the passage of time. Therefore,traditional medicines are not only a valu-
ableculturalheritageofmankind,butalsoarichresourceformoderndrug
development.Throughtheages,naturehasbeenasourceandcontinuesto
betheproviderofdrugsforavarietyofailments.
To understand the link between chemicals from nature and human
health,itisimportanttoknowtheecologyof theareaof thedrugsource.
v
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vi Biodiversity,NaturalProductsandCancerTreatment
Plantsaswellasmanymarineorganismssuchassponges,coralsandtuni-
catesaresessileandliveinthesameenvironmentwithpathogenicbacteria,
virusesandherbivores.Todefendthemselves,theyproducephytoalexinsor
antibiotics,providingapossiblelinkbetweenchemicaldefenseagainstsuch
harmfulorganismsanddrugsforuseinhumans.Marineproductshavelong
beenusedintraditionalmedicineinTaiwan,Japan,ChinaandIndiaandit
has been known for centuries that sponges are a source of medicinally
important compounds. Plants such as Glycyrrhiza glabra, Commiphora
species,andPapaversomniferum,usedtodayformedicinalpurposes,were
alreadyusedinMesopotamia2600yearsbeforetheChristera.TheWorld
Health Organization (WHO) estimated in 1985 that approximately 65%
of the population of the world predominately relied on plant-derived
traditional medicines for their primary healthcare; meanwhile, phyto-
chemicals or their synthesized derivatives still play an important role in
drugdiscovery.
Examples of pharmaceuticals include the bronchodilator, chromolyn
(which originated from the phytochemical, khellin, a furanochromone
from Ammi visnaga (L) Lamk.); the antihypertensive verapamil (which
originated from papaverine,an opium alkaloid antispasmodic drug from
Papaversomniferum);thewell-knownantimalarialdrug,quininefromCin-
chona trees); and the sesquiterpene lactone artemisinin from Artemisia
annua. Plants have also been used in the treatment of cancer and have
affordedanti-proliferativedrugsinclinicaluse,suchastheVincaalkaloids,
vinblastineandvincristinefromtheMadagascarperiwinkle,Catharanthus
roseus;andetoposideandteniposide,whicharesemi-syntheticderivatives
of the natural product, epipodophyllotoxin, from Podophyllum peltatum.
There is also a large chemical and biological diversity of the different
marine evolutionary group, making them a remarkable resource for the
discovery of new drugs, including anti-neoplastic agents. Products from
marinefloraandfaunahaveinthepastbeenusedinthetreatmentofvar-
ioushumanailments.Severalcompoundsfrommarineorganismssuchas
sponges,coelenterates and microorganisms as well as echinoderms,tuni-
cates,mollusks,andbryozoansareasourceof anticancerdrugs.Examples
ofestablisheddrugfrommarineorganismsincludethewellknownAra-A
andAra-C(respectively,antiviralandanticancerfrommarinesponge)and
thecephaolosporinsantibioticsfrommarinefungi.Otheranticancerdrugs
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Preface vii
in the clinical phase include LAF389 from sponge (phase I), YondelisTM
from sea squirt (phase II/III), Cemadotin from sea slug (phase II), and
ILX651andDolastatin-10fromseaslug(phaseII).
Fromourpointofview,itmakesmuchsensetobringtogetherscientists
fromdifferentdisciplines,e.g.medicine,pharmacology,organicchemistry,
molecular biology, gene and biotechnology, botany, ethnobotany, phyto-
chemistry,microbiology,oceanography,andotherrelatedfieldstoworkon
an interdisciplinary field such as biodiversity. This point of view is sup-
ported by the fact that biodiversity, natural products and cancer therapy
have become thriving fields of research attracting numerous scientists. A
comprehensive survey of published papers from 1990 to 2012 shows that
suchfieldsofresearchhavebeengrowingovertime(Fig.1).
Theadventofmolecularbiologyhasrevolutionizedalmostallfieldsin
the life sciences. This is a very illustrative example that inter- and cross-
disciplinaryapproachesdonotonlycross-fertilizethevariousdisciplines,
but also can lead to scientific revolutions and major breakthroughs with
gain of new knowledge. At our universities, we are frequently faced with
tightlypackedcurricula,resultinginalackof roomfortopicsoutsidethe
Figure 1 Survey of the literature documented in the PubMed database from 1990 to
2012withthekeywords“biodiversity”and“naturalproductsandcancertherapy.”
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viii Biodiversity,NaturalProductsandCancerTreatment
classical teaching content. Inter- and cross-disciplinary topics are mostly
notsufficientlyrepresentedinacademicteaching.Therefore,wefeltthatit
isnecessarytofurtherstrengtheninter-andcross-disciplinaryresearchand
teaching and try to span a bow from biodiversity to cancer therapy with
severalofitsmajortopics.
Thehighlightofthisbookisanexhaustivecompilationofscientificdata
onBiodiversityof medicinalplants(Chapter1),Biodiversityandmetage-
nomics (Chapter 2), Chemical ecology of medicinal plants (Chapter3),
Chemical ecology of marine organisms (Chapter 4), Natural products
from terrestrial microbial organisms with activity towards cancer cells
(Chapter5),Marineorganisms(Chapter6),Ethnopharmacologyandphy-
totherapy(Chapter7),ContributionofAfricanfloraintheworldwidefight
againstcancer(Chapter8),Naturalproductsderivedfromterrestrialplants
with activity towards cancer cells (Chapter 9),and Established anticancer
drugsfromnaturalorigin(Chapter10).
These topics have been chosen for seminars in the Pharmacy and
Molecular Biotechnology programs at the Universities of Mainz and Hei-
delberg,Germanyduringthepastfewyears.Studentshavechosentopicsof
theirinterests,preparedpapersbasedonup-to-dateknowledgetakenfrom
literatureandpresentedthemtotheplenum.Hence,theexistingcurricula
have been used to establish possibilities for inter- and cross-disciplinary
topics,whichareof highrelevancenotonlyforresearchandeducationin
pharmacy and biotechnology,but also in related fields such as molecular
medicine,pharmacology,drugdevelopment,medicinalchemistry,molec-
ularbiologyetc.
Indoingso,studentsacquirednotonlyknowledgebutalsoasensehow
fertileinter-andcross-disciplinaryresearchcanbe.Thismightbehelpful
intheirlaterprofessionallife.
The book discusses the state-of-the-art of each documented topic
to serve as a reference resource tool for scientists and scholars in
pharmaceutical sciences,pharmacology,organic chemistry and biochem-
istry,pharmacognosy,phytochemistry,ethnomedicineandethnopharma-
cology,complementaryandalternativemedicine,medicalandpublichealth
sciencesandothers.
In 2007,one of the editors (TE) met Dr. Ben terWelle (Georgetown,
Guyana)duringanexpeditionintherainforestsof Guyana.DrterWelle’s
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Preface ix
excellentknowledgeoftheplantsandecologyoftherainforestwasimpres-
siveandgavethemotivationforabookwhichbringstogetherbiodiversity,
chemicalecology,phytochemistryandcancertherapy.Withouthisinspir-
ing love of nature,the idea to write a book like this would not have been
born.Thankyou,Ben!
WearealsogratefultotheScientificEditor,Sook-ChengLimandher
teamfromWorldScientificPublishing.Therealizationofthisbookwould
not have been possible without their support and patience. Furthermore,
we thank Karen Duffy (Cornell University, Ithaca, NY, USA) for reading
andcorrectingthemanuscriptsasanativespeaker.Aspecialthanksalsoto
IlonaZirbsforhersecretarialsupportinpreparingthemanuscripts.
VictorKueteandThomasEfferth
Mainz,October2013
