Cancer—an ayurvedic perspective - AIP

12 Pages·2004·0.13 MB·English

PharmacologicalResearch51(2005)19–30
Cancer—an ayurvedic perspective
Premalatha Balachandrana,∗, Rajgopal Govindarajanb
aNationalCenterforNaturalProductsResearch,DepartmentofPharmacognosy,UniversityofMississippi,MS38677,USA
bDepartmentofBiochemistryandMolecularBiology,UniversityofNebraskaMedicalCenter,Omaha,NE68198-4525,USA
Accepted23April2004
Abstract
An integrated approach is needed to manage cancer using the growing body of knowledge gained through scientific developments.
Thousandsofherbalandtraditionalcompoundsarebeingscreenedworldwidetovalidatetheiruseasanti-cancerousdrugs.Thescienceof
Ayurvedaissupposedtoaddastepontothecurativeaspectsofcancersthathaveresemblancewithclinicalentitiesofarbudaandgranthi
mentionedinSushruthasamhita.Hence,anattemptismadeinthisreviewtodiscussaboutthepathologyandtherapeuticmanagementof
variouscancersdescribedinAyurveda.Reviewofliteratureonanticancerdrugsofplantoriginrevealedidentificationofnewerayurvedic
drugsthatarenotmentionedintheancienttexts.Thesenewfindingsadduptoayurvedicsciencethathasbeendevelopedthroughages.
Inaddition,detailsofexperimentalandclinicalstudiesconductedonsingleandcompoundayurvedicpreparationsfortheiranticancer
efficacystronglyemphasizeayurvedictherapyasascientificallydrivenoneandnotsimplyunconventional.
©2004ElsevierLtd.Allrightsreserved.
Keywords:Cancer;Ayurveda;Treatment;Medicine;Herbal
1. Introduction The broad aim of this article is to provide a general out-
line on descriptions of cancers and their management from
Cancer is one of the most dreaded diseases of the 20th anayurvedicpractitioners’perspectiveunderlyingitsscien-
centuryandspreadingfurtherwithcontinuanceandincreas- tificprinciplesinvolvedintreatingtheseconditionswiththe
ing incidence in 21st century. In the United States, as the use of natural products. This article reviews the available
leadingcauseofdeath,itaccountsfor25%ofallthedeaths literature regarding researches on anti-cancerous ayurvedic
in humans presently. It is considered as an adversary of herbs and also includes a summary of treatment strategies
modernization and advanced pattern of socio-cultural life for various cancers. It is written with an intention to raise
dominatedbyWesternmedicine.Multidisciplinaryscientific awarenessandencourageimplementationofayurvedicther-
investigationsaremakingbesteffortstocombatthisdisease, apiesforcombatingcancerandsuggestinganintegratedap-
butthesure-shot,perfectcureisyettobebroughtintoworld proachintumourmanagementandtreatment.
medicine.
Recently, a greater emphasis has been given towards the 1.1. Ayurvedicconceptofcancer
researches on complementary and alternative medicine that
deals with cancer management. Several studies have been Charaka[11]andSushruta[12]samhitas,twowell-known
conducted on herbs under a multitude of ethno botanical Ayurvedic classics, describe cancer as inflammatory or
grounds. For example, Hartwell [1–9] has collected data non-inflammatory swelling and mention them as either
on about 3000 plants, those of which possess anticancer Granthi (minor neoplasm) or Arbuda (major neoplasm).
properties and subsequently been used as potent anticancer Ayurvedic literature defines three body-control systems,
drugs[10].Ayurveda,atraditionalIndianmedicineofplant viz., the nervous system (Vata or air), the venous system
drugs has been successful from very early times in using (Pitta or fire), and the arterial system (Kapha or water)
these natural drugs and preventing or suppressing various which mutually coordinate to perform the normal function
tumoursusingvariouslinesoftreatment. ofthebody.Inbenignneoplasm(Vataja,PittajaorKaphaja
) one or two of the three bodily systems are out of control
and is not too harmful because the body is still trying to
∗Correspondingauthor.Tel.:[phone];fax:[phone]. coordinate among these systems. Malignant tumours (Tri-
E-mailaddress:[email protected](P.Balachandran). dosaja)areveryharmfulbecauseallthethreemajorbodily
1043-6618/$–seefrontmatter©2004ElsevierLtd.Allrightsreserved.
doi:10.1016/j.phrs.2004.04.010
20 P.Balachandran,R.Govindarajan/PharmacologicalResearch51(2005)19–30
systems lose mutual coordination and thus cannot prevent f. Medoaggravatingfactors:excessiveintakeofoilyfoods,
tissuedamage,resultinginadeadlymorbidcondition[12]. sweets,alcoholandlazyattitude[11,12].
1.2. Fundamentalclassification 1.4. Pathogenesisoftumours
Ayurvedicclassificationofneoplasmdependsonvarious AccordingtoAyurvedicprinciples,thediseasecannotbe
clinicalsymptomsinrelationtoTridoshas. namedonitsownbecauseitdiffersbetweenpersonsinterms
of illness, clinical presentation and also the treatment re-
GroupI: Diseasesthatcanbenamedasclearmalignancy, quired[14].Thus,pathogenesisinAyurvedaisexplainedon
whichincludesarbudaandgranthi,e.g.mamsar- thebasisofTridoshas.AgniorPitta,whichispresentineach
buda (melanoma) and raktarbuda (leukaemia), andeverycell,isresponsiblefordigestionandmetabolismin
mukharbuda(oralcancer),etc. humanbody.Thedecreaseinagniisinverselyproportional
GroupII: Diseases that can be considered as cancer, such to the related tissue and therefore in arbuda, the decreased
asincurableulcerswithe.g.tridosajgulmas(ab- stateofdhatwagni(derangedmetabolism)willresultinex-
dominaltumourslikecarcinomasofthestomach cessivetissuegrowth.
andliverorlymphomas). Vatacanbecorrelatedwiththeanabolicphaseofgrowth
GroupIII: Diseaseswiththepossibilityofmalignancy,e.g. whereaskaphatothecatabolicphase.Canceroriginatesdue
Visarpa(erysipelas),asadhyakamala(incurable toametaboliccrisis,i.e.aggravationofvataforcesandsup-
jaundice)andnadivrana(sinusitis)[13,14]. pression of kapha forces, both interacting with one another
resultinginproliferation.However,theabnormalcancerous
1.3. Etiology growth at a specific organ (Ekadesavriddhi) is managed by
compensationfromotherpartsofthebody(Anyasthaniyak-
According to Sushruta, the fundamental cause of major shaya),e.g.bodyweightloss(cachexia) [17].Sushrutahas
neoplasm is the pathogens that affect all parts of the body. proposed six stages in the pathogenesis of all diseases but
Hecalledthesixthlayeroftheskinas‘Rohini,’(epithelium) his concept suits more to the pathology of the tumour than
andpathogenicinjuriestothislayerinmusculartissuesand pathogenesisitself.
blood vessels caused by lifestyle errors, unhealthy foods,
1. Sanchaya:earlystagesoflocalizedneoplasticchanges.
poor hygiene and bad habits results in the derangement of
2. Prakopa: transformation of primary growths into
doshas,whichleadstothemanifestationoftumours[12,15].
metastatictumours.
Excess of water or fat in the corpus of the tumour and the
3. Prasara:metastasis.
stabilityandrigidconfinementofthedoshasinaparticular
4. Sthana samsraya: complete metastasis and secondary
place were described as reasons for the non-infectious and
growth.
non-suppurative nature of these abnormal growths [12,16].
5. Vyakti:clinicalsignsandsymptomsareexpressed.
Cancer in each person differs according to the person’s ex-
6. Bheda: the stage where differentiation of growth occurs
posure to pathogens and genetic constitutions which make
onthebasisofhistopathology[17].
eachofthemtoreactdifferentlytothesamediet.
The factors responsible for the vitiation of doshas are
discussedhere[17].
2. Cancertherapy—apracticaldilemma
a. Vataaggravatingfactors:excessiveintakeofbitter,pun-
gent,astringent,dryfoodsandstressfulconditions. Anypracticalsolutionincombatingthisdreadfuldisease
b. Pittaaggravatingfactors:excessiveintakeofsour,salty, isofparamountimportance.Analternativesolutiontowest-
friedfoodsandexcessiveanger. ern medicine embodied with severe side effects is the use
c. Kapha aggravating factors: excessive intake of sweet, ofmedicinalplantpreparationstoarresttheinsidiousnature
oilyfoodandsedentarynature. of the disease. Many herbs have been evaluated in clinical
d. Rakta aggravating factors: excessive intake of acid or studiesandarecurrentlybeinginvestigatedphytochemically
alkali containing foods. Fried and roasted foods, alco- tounderstandtheirtumouricidalactionsagainstvariouscan-
holicbeverages,sourfruitsaresomeexamples.Excessive cers. Thus, cancer patients who already got crippled with
anger or severe emotional upset, sunbathing or working thisdisease,furtherburdenedbydrug-inducedtoxicsideef-
under scorching sun or near fire and hot conditions, etc. fectshavenowturnedtoseekhelpfromthecomplementary
aresomeothercauses[11]. andalternativemedicinehopingforabettercure.Ayurvedic
e. Mamsa aggravating factors: excessive use of exudative therapy was found to be able to cure these chronic dis-
foods like meat, fish, yoghurt, milk and cream. Be- eases better, which were previously not amenable to treat-
haviours leading to exudation like sleeping during the ment by western medical practices. This traditional Indian
dayandovereatingaresomeofthecausesforpathogens medicine with its evolution through centuries has always
invadingthefattytissues[11]. fascinated practitioners and researchers for its applications
P.Balachandran,R.Govindarajan/PharmacologicalResearch51(2005)19–30 21
incancertreatmentonascientificallyprovenresearchback- Rasayana prayoga (immunotherapy), certain poisonous
ground. plants, mercury like metals and animal products were ren-
derednon-toxicandharmlessbytheuseofalchemyandare
2.1. Principlesofayurvedictreatment used as rejuvenating drugs. Other methods of treatment in-
clude,dhatwagnichikitsa(correctionofmetabolicdefects),
Abuseofnature’slawupsetsthehumansystemandends vyadhipratyanika chikitsa (specific anti-cancerous drugs)
upindiseaselikecancer.Itisagainthenature,theforemost andlakshanikachikitsa(symptomatictreatment)[24].
physician who brings the cure. The Ayurvedic system of Whenmedicaltreatmentpracticesfail,thenthecasewas
medicinewaswellfoundedonthebasicprinciplesofnature left to surgeons. Surgical cancer management in Ayurveda
anditselementsafteracarefulandthoroughstudyofhuman include the principles of fomentation by means of external
physiology.Thisisthefirstsystemtoemphasizehealthasthe application, cleansing by internal medication, treatment to
perfect state of physical, psychological, social and spiritual liquefythecontentsoftheswelling,openingthetumoursur-
componentofahumanbeing. gicallyforevacuationofitscontents,cauterisationtoavoid
The therapeutic approach of Ayurveda has been di- recurrence and post-operative care for healing the wound
vided into four categories as Prakritisthapani chikitsa [15].
(health maintenance), Roganashani chikitsa (disease cure), Cauterisationwithalkalisandacidsandothersurgicalpro-
Rasayana chikitsa (restoration of normal function) and cedureswereperformedwithherbalandmineralmedicines.
Naishthikichikitsa(spiritualapproach)[18]. Arbuda is excised completely from its deep root seat and
Finding the cause of an illness is the basic goal of cauterisationdonetodestroyanyoftheremainingcellpar-
ayurvedictherapy.Itclassifiesdiseasedevelopmentintosix ticles[24].
stagesthatincludeaggravation,accumulation,overflow,re-
location,build-upinanewlocation,andmanifestationinto 2.4. Classicaldrugsclaimedinayurvedictexts
a recognizable disease. Ayurvedic physicians can diagnose
anillnessateveninitialstagesofbodyimbalanceandtheir Traditional line of treatment: Traditional methods em-
therapeutic approach maintains a balance by supplying de- ployedintreatmentofvariouscancersweregiveninTable1.
ficient substances as well as reducing the excessive ones. Inadditiontothesetraditionalmethods,variousherbalcom-
Surgeryisconsideredonlyforadvancedcases. binationsmentionedinAyurvedictextsarelistedinTable2.
The main objective of these tables is to support the physi-
2.2. Ayurvedictextsaboutcancertreatment ciansandresearcherstoutilizethesetraditionalmethodsas
wellasherbaldrugsforaneffectivecancertreatment.
Duringthe7thcenturyBC,AtreyaandDhanwantariused
herbalmedicinesfortreatingtheearlystagesofcancerand 2.5. ScientificprinciplesofAyurvedicanticancerdrugs
surgery in advanced cases. In the 8th century AD, Vagb-
hata,aBuddhistphysiciancomposedtwotexts:AstangaHr- Herbaldecoctionsconsistingofmultipleherbseachpos-
daya [19] and Astanga sangraha [20] where new methods sessingtremendouspotentialforacancercurearecommonly
forcancertreatmentwereintroduced.OtherAyurvedictexts used in Ayurveda. These formulations are reported to work
of internal medicine, viz., Chakradatta [21] composed by onmultiplebiochemicalpathwaysandarecapableofinflu-
Chakrapani (10th century AD), the Sarangadhara Samhita encingseveralorgansystemssimultaneously.Thebenefitof
[22]bySarangadhara(14thcenturyAD),theBhavaprakasha anherbaldecoctionisthatitcannourishthebodyasawhole
Samhita [23] by Bhavamisra (15th century AD), the Sat- bysupportingvariousorgansystems[25].Manyoftheherbs
mya Darpan Samhita by Viswanath (16th century AD), the mentioned below have scientifically-proven anti-cancerous
VaisajyaRatnabalibyBinodaLalaSenGupta(18thCentury propertiesandareusedforthetreatmentofvariouscancers.
AD),theRasataranginibySadanandaSharma(19thcentury
AD), etc. explain numerous remedies to treat internal and 2.6. Andrographispaniculata
externalneoplasms.
The extract and isolated diterpenes (andrographiside and
2.3. Treatmentmodalities neoandrographolide) from this plant are proved to be ben-
eficialagainsttumourigenesisbytheiranti-lipoperoxidative
Sodhana chikitsa (purification process), which elimi- action and by enhanced carcinogen detoxification action
natesvitiateddoshas,havebeenprimarilyusedformedical [26–29].
management of cancer. When both internal and external
medications were given then it is called as panchakarma 2.7. Annonaatemoya/muricata
chikitsa.Theothertypeofcurativetherapyiscalledsomana
chikitsa,whichpacifiesdoshaandgraduallyrelievesthedis- Bullatacin, an acetogenin isolated from the fruit of An-
ease. However, this treatment is prescribed only to weaker nona atemoya, induces apoptosis, preceded by chromatin
patients for whom sodana chikitsa is contraindicated. In margination and tumour cells condensation [30]. Several
22 P.Balachandran,R.Govindarajan/PharmacologicalResearch51(2005)19–30
Table1
ClassicaltreatmentprotocolsforvarioustumoursinAyurveda
Typeoftumour Tumoursubtypes Classicaltreatmentprocedures
Granthi Vatikagranthi Helloborusniger,Tinosporacordifolia,Clerodendronserratum,Aeglemarmelos,Hoya
viridiflora,Elephantopusscaber,SoymidafebrifugaandGynandropispentaphyllawere
appliedlocally[16]
Paittikagranthi Terminaliachebulapowderwitheithergrapeorsugarcanejuicewereusedorally.The
pasteofGlycyrrhizaglabra,Eugeniajambolana,TerminaliaarjunaorCalamusrotang
wereusedofexternalapplication[16]
Kapajagranthi PasteofCapparisspinosa,Capparissepiaria,Agatigrandiflora,Lagenariavulgaris,
Premnaherbacea,Pongamiaglabra,MusasapientumandRandiadumetorumusedin
localapplication[16]
Arbuda Classicalprocedures Fomentations,cauterisation,scraping,bloodletting,medicatedenemataandothersurgical
procedures[17]
Traditionaltreatment HabitualintakeofBasellarubraorapplicationofalkalipreparationofMusaparadisiaca,
Conchshellash,Elaeocarpustuberculatus,Sulphur,Potassiumcarbonate,Embeliaribes
andgingerwereusedtocurearbuda[16]
Vatajaarbuda PasteofBenincasacerifera,Cucumismemordica,Cocosnucifera,andErandabeeja,
Ricinuscommunisalongwithbutterormilkwereapplied[65]
Pittajaarbuda TumoursweretreatedwithleavesofFicusglomerata,Tectonagrandis,andElephantopus
scaberrepeatedlyandthenwithahoneymixedfinepasteofAglajaroxburghiana,
Caesalpiniasappa,Symplocosracemosa,Terminaliaarjuna,Xanthiumstrumariumwas
applied[16]
Kaphajaarbuda Aftersurgicalremovaloftumour,adrugthatremovedoshasfromboththeends(vomiting
andpurgation)wereemployed.Thenforpurification,adecoctionofClitoriaternatea,
JasminumgrandiflorumandNeriumodorumleaveswasused.Forthepostoperativecare,
oilcookedwithPremnaherbacea,Embeliaribes,Cissampelospareirawasapplied
Medojaarbuda Curcumadomestica,Triticumsativum,Symplocosracemosa,etc.weremadeintoapowder
andappliedexternallybymixingthemwithhoney.OilfromPongamiaglabrawereused
ofinternaladministration[65]
Table2
Listofherbscommonlyusedinayurvedicanticancertreatment
No. Nameoftheherb Methodanduse
1 Vitisvinifera ThemixtureofTerminaliachebula,grapejuiceandsugarcanejuicehasbeenused(3).
Resveratrol,anaturalproductderivativefromgrapejuicehasbeenprovedtopossesscancer
chemopreventiveactivity[66]
2 Baliospermummontanum ThepastecomprisingofBaliospermummontanum,Plumbagozeylanica,Euphorbianeriifolia,
Calotropisprocera,jaggery,Semecarpusanacardiumappliedoverthetumours[12]
3 Madhucaindica ThispasteispreparedfromthebarksofMadhucaindica,Syzygiumcumini,arjunaTerminalia
arjunaandSalixcapreaandprescribedforlocalapplication[12]
4 Pandanusodoratissimum ApasteofPandanusodoratissimumwithsugarwasappliedexternally[12]
5 Pterospermumacerifolium TheflowersofPterospermumacerifoliummixedwithsugartobeappliedlocally
6 Raphanussativus LocalapplicationofRaphanussativuspowderpastewiththeradishashwasconsidered
effectiveagainstkaphajaarbuda
7 Barleriaprionitis TheBarleriaprionitisoilpreparedwithwholeplantisindicatedforexternalapplication
duringacutestagesofcystinbloodvessels[20]
8 Prosopiscineraria ThispastemadeupofProsopiscinerariaseeds,Raphanussativa,Moringaoleifera,barley
andmustardwithsourbuttermilkwasappliedlocallyfordisintegratingcysts [20]
9 Amorphopalluscampanulatus Thematuretuberisfirstburntandthenmixedwithbutterandjaggeryandappliedfortumour
destruction[12]
10 Oxoxylumindicum ThedrugOxoxylumindicumprescribedintreatmentofgranthi[12]
11 Basellarubra Theplantandleavesaregroundwithsourbuttermilkwithsaltforpreparingapoulticeand
indicatedforarbuda[12]
12 Flacourtiaromantchi ThepasteofFlacourtiaromantchi,Cassiafistula,Capparissepiaria,isrecommendedfor
kaphajatumours[12]
13 Moringaoleifera ThepasteofMoringaoleiferaseeds,Solanumxanthocarpum,Sinapisdichotoma,Holarrhena
antidysentericaandNeriumodorumrootspreparedwithbuttermilkisusedforarbuda
tumours[23]
14 Ficusbengalensis ApplicationofmixtureofFicusbengalensisandSaussurealappapacifytumourgrowthon
bone[23]
15 Curcumadomestica TheCurcumadomesticapowderincombinationwithSymplocosracemosa,Soymida
febrifuga,ismixedwithhoneyandthisisusedasanexternalremedy[23]
P.Balachandran,R.Govindarajan/PharmacologicalResearch51(2005)19–30 23
other annonaceous acetogenins, e.g. muricins A–G, muri- immunosuppression and hence could be a drug choice for
catetrocinAandB,longifolicin,corossolin,andcorossolone variouscancers.
are also showed to be significantly selective in bringing in
vitrocytotoxicitiestotumourcells[31]. 2.12. Semecarpusanacardium
2.8. Phyllanthusniruri/amarus In Ayurveda classics, numerous references are available
on the anticancer properties of Semecarpus anacardium
AnaqueousextractofP.amarusincreasesthelifespanof nuts[43].Anextensivereviewdescribesthephytochemical
thetumourbearingratsandnormalizes(cid:1)-glutamyltranspep- andpharmacologicalpropertiesofS.anacardium[44].The
tidase activity [32]. It plays a major role in disruption of chloroformextractofS.anacardiumnutpossessantitumour
HBsAg mRNA transcription and post-transcription which actionwithincreasedlifespanagainstleukaemia,melanoma
couldbebeneficialagainstviralcarcinogenesis[33]. and glioma [45,46]. The milk extract of S. anacardium
produces regression of hepatocarcinoma by stimulating
2.9. Piperlongum host immune system [47] and normalizing tumour markers
including alpha-fetoprotein levels [48,49]. This prepara-
Piperine, an active alkaloid extracted from this plant has tion stabilizes the lysozomes, and normalizes glycoprotein
been used as an ingredient of ayurvedic anticancer formu- and mineral content in the body during cancer progression
lationsbecauseofitsanti-oxidativepotencyinbothinvitro [50,51]. It also corrects hypoglycaemia [52] and controls
andinvivoconditions[34]. abnormallipidperoxidation[53]bythemaintenanceofan-
tioxidant defense status [54]. In the microsomes, it acts as
2.10. Podophyllumhexandrumlinn.(Podophyllin) abifunctionalinducerofbothphaseIandIIbiotransforma-
tion enzymes and prevents tumour initiation by preventing
Itisapowerfulanticancerdrugagainstvariouscancersfor carcinogen activation [55,56]. Histologically, on treatment
e.g.sarcomas,adenocarcinomaandmelanoma.Podophyllin withtheS.anacardiumextracttohepatocarcinomaanimals,
anditsactiveprinciple,podophyllotoxinareknownfortheir theliversectionsshowedalmostanormalarchitecture.The
cytotoxic effect by virtue of their properties of mitotic in- nodulesbecomecompletelyregressedandfurthercellnecro-
hibition,nuclearfragmentation,impairedspindleformation siswasprevented[57].Anacartinforte,anotherpreparation
and they are also found to be karyoplastic. The mechanism fromS.anacardiumhasbeenusedforseveraldecadesasan
ofactionhasbeensuggestedasnecrosisandisadirectcon- anticancer drug since it is giving health improvement with
sequence of its cytotoxic effect on tumour tissues. These alleviation or disappearance of troublesome symptoms. It
derivatives have been analysed in cancer chemotherapeutic provides clinical benefit with an extension of survival time
studiesandthemethodsofpreparationofthesecompounds in various cancers including oesophageal, chronic myeloid
arepatented[10]. leukaemia, urinary bladder and liver cancer [58]. Another
Inrecentdays,chemicallymodifiedpodophyllotoxinsare AyurvedicdrugcontainingS.anacardium,Amurarohitaka,
widely used in cancer therapeutics. VP-16 (etoposide), a Glycyrrhiza glabra and copper powder were reported to
podophyllotoxin derivative has been tested against in vitro inhibit breast tumour development in mice by significantly
andinvivocancercellsandbeenusedagainsthepaticcan- extending the survival period. This drug was also found to
cers for more than a decade [35]. It has proved its efficacy beefficientinclinicaltrials[13].
in combination with epirubicin in phase II studies [36,37]. Ayurvedic herbs, which are widely used and scientifi-
Bythiscombinationtherapyatleast3%ofthepatientshad cally proven of their anticancer properties, are presented
completecureand36%hadpartialresponse.P-glycoprotein, in Table 3. Smit et al. [59] have also elaborately listed
a drug efflux pump, seems to be less effective in reducing ayurvedic herbal drugs with anticancer activity. Some of
VP-16concentrationincancercelllinesandhencethisdrug these herbs are shown to enhance the therapeutic efficacy
provestobemoreefficientinthesecells[38].Itisalsosafe and/or reduce the toxicity of anticancer drugs used in
even above therapeutic dosage without much toxic effects chemotherapy.Alsofewofthempossessradiosensitisingef-
[39]. fecttoo(seeTable4).Pharmacologicaldetailsofayurvedic
herbs like therapeutic dosage, side effects, and comments
2.11. Tinosporacordifolia about safety and herb-drug interactions were given in
Table5.
The active principles from T. cordifolia enhance host
immune system by increasing immunoglobulin and blood
leukocyte levels and by the stimulation of stem cell prolif- 3. Potential benefits of Ayurveda during
eration.Ithastheabilitytoreducesolidtumourvolumeby Cancercachexia
58.8%,whichiscomparabletocyclophosphamide,aknown
chemotherapeuticagent[40–42].Theseimmunostimulating Cancer cachexia is a common clinical problem that sub-
propertiescanbeusedinthepreventionoftumourmediated stantially impacts upon the quality of life and survival of
24 P.Balachandran,R.Govindarajan/PharmacologicalResearch51(2005)19–30
Table3
ScientificevidenceonherbsusedinAyurvedaproventohaveanticancerproperty
Nameoftheherb Indications References
Abrusprecatorius Yoshidasarcoma(rats) SubbareddyandSirsi[67]
Fibrosarcoma(mice)
Ascitestumourcells
Albizzialebbeck Sarcoma180(mice) Dharetal.[68]
Alliumsativum Sarcoma(rat) Huetal.[69]
Aloevera YoshidaAH-130ascitehepatoma(pleuraltumour) Corsietal.[70],Pecereetal.[71]
humanneuroectodermaltumours
Alstoniascholaries HSIhumansarcomabenzo(a)pyreneinduced Dharetal.[68],Jagetiaetal.[72]
forestomachcarcinoma
Amurarohitaka Leukaemia PrasadandDeshpande[73],RabiandGupta[74]
Anacardiumoccidentale Hepatoma129 Dharetal.[68]
Asparagusracemosa Humanepidermoidcarcinoma Dharetal.[68]
Bacopamonniera Walkercarcinosarcoma256 Bhakunietal.[75]
Berberisaristata Humanepidermalcarcinomaofthenasopharynx Bhakunietal.[75],Anisetal.[76]
N-nitrosodiethylamineinducedcarcinogenesis
Boswelliaserrata Humanepidermalcarcinomaofthenasopharynx Dharetal.[68]
Leukaemiaandbraintumours Hostanskaetal.[77]
Calotropisgigantea Humanepidermalcarcinomaofthenasopharynx Bhakunietal.[75],Dharetal.[68]
Curcumalonga Fibrosarcoma SriganthandPremalatha [78]
Preclinicalandclinicaltrialsreview Aggarwaletal.[79]
Daturametel Humanepidermalcarcinomaofthenasopharynx Dharetal.[68]
Erythrinasuberosa SARCOMA180 Dharetal.[68]
Euphorbiahirta Freundvirusleukaemia Dharetal.[68]
Gynandropispentaphylla Hepatoma129 Dharetal.[68]
Heliotropiumindicum P-388lymphocyticleukaemia Paletal.[80]
Hygrophilaspinosa Dalton’slymphoma Maiti[81]
EhrlichascitescarcinomaandSarcoma-180 Mazumdaretal.[82]
Ixoraundulata P-388lymphocyticleukaemia Dhawanetal.[83]
Juniperusindica Humanepidermoidcarcinomaofthenasopharynx Dhawanetal.[83]
Luffacylindrica Schwartzleukaemia Bhakunietal.[84]
Meliaazedarach Walkercarcinosarcoma256 Bhakunietal.[75]
Moringaoleifera Humanepidermoidlymphocyticleukaemia Dhawanetal.[83]
Skinpapillomagenesis Bharalietal.[85]
Neriumindicum Erlishascitescarcinoma Paletal.[80]
Nigellasativa Lewislungcarcinoma Dharetal.[68]
Coloncancer SalimandFukushima[86]
Ocimumsanctum Skinandlivertumours Dubeyetal.[87]
Paederiafoetida Humanepidermoidcarcinomaofthenasopharynx Dharetal.[68]
Picrorrhizakurroa Hepaticcancers Dharetal.[68]
Plumbagozeylanica Hepatoma ParimalaandSachdanandam[88]
Rubiacordifolia P-388,L-1210,B-16melanoma,colon388,Lewis Itokawaetal.[89]
lungcarcinoma,mammarycarcinoma
Taxusbuccata Cytotoxicagainstvarioustumours Meladoetal.[90]
Vincarosea P-1534,carcinomaofthebreast,cervix,kidney,lung RastogiandMehrotra[91]
andovary
Withaniasomnifera Varioustumours Dharetal.[68]
cancer patients. The pathophysiology of this syndrome im- side effects and cancer associated complications. It also
plicatestumourinducedmetabolicchangesandimmunere- avoids the need for supplemental therapy to manage can-
sponses. Clinical manifestations include anorexia, chronic cer cachexia. Each herbal product contains multiple active
nauseaandchangeinbodyimage.Amongseveralpotential principles that may operate synergistically, producing ther-
benefitsofayurvedicmedicine,relieffromcancercachexia apeuticbenefitsandloweringtherisksonadverseeffects.
isespeciallyvaluable.Ayurvedicherbsusedincancerther- The anorexia or weight loss could be effectively man-
apy results not only in total healing, but also reduces the aged by Withania somnifera, Sida cordifolia, Asparagus
P.Balachandran,R.Govindarajan/PharmacologicalResearch51(2005)19–30 25
Table4
Therapeuticenhancementpotentialofayurvedicherbsoncancerchemotherapy/radiation
Nameoftheherb Chemotherapy/ayurvedicherbinterventionstudies
Alliumsativum Water-solublederivativeofgarlic,S-allylmercaptocysteine(SAMC),inhibitedproliferationandcellcycle
progressionintwohumancoloncancercelllines,SW-480andHT-29,similartotheeffectsofsulindac
sulfide(SS),awell-knowncoloncancerchemopreventiveagent.Co-administrationofSSwithSAMC
enhancedthegrowthinhibitoryandapoptoticeffectsofSS,suggestingtheusefulnessofSAMCaloneorin
combinationwithSSorotherchemopreventiveagents[92]
Aloevera Inarandomiseddouble-blindedclinicaltrial,comparingmildsoapandaloeveragelagainstincidenceof
radiationtherapyinducedskinreactions,themediantimeoffiveweekswastakentoshowanyskinchanges
inthealoe/soaptreatmentversusthreeweeksinthesoaponlytreatment.Theprotectiveeffectofadding
aloetothesoapregimenincreasesduringlongtimeradiationexposure [93].Inanotherclinicaltrial
involvingpatientswithadvancedsolidtumours,forwhomnootherstandardeffectivetherapywasavailable,
combinationofpinealindolemelatonin(MLT)plusAloeveraextractsproducedsometherapeuticbenefits,
atleastintermsofstabilizationofdiseaseandsurvivalwhencomparedtoMLTalonetreatment [94]
Alstoniascholaris TheAlstoniascholarisextractpre-treatmentincreasedtheeffectofradiationasbyenhancementofcell
killinginHeLaandKBcells,followedbyHL60,MCF7,andHePG2cells.Ininvivostudies,withEhrlich
ascitescarcinomabearingmicethepre-treatmentofextractcausedincreasedlifespanofanimalswhen
comparedwithuntreatedirradiatedgroup[95].ThecombinationtreatmentofAlstoniascholarisextractwith
cyclophosphamidewasalsofoundtobemosteffectiveagainstEhrlichascitescarcinomaasitcausedthe
highesttumourregressionandenhancedthemeanandaveragesurvivaltimewhencomparedwith
cyclophosphamidealonetreatedgroup[96]
Curcumalonga Whenradiationandcurcumawereappliedtogetherassynergicaltherapy,curcumashowedaradiation
sensitisingeffectinHeLa,K-562andIM-9celllines[97].Curcumin,theactiveconstituentfromCurcuma
longaalsoenhancestheanticancerpotentialofCisplatinandreducesitsnephrotoxicityinfibrosarcoma
bearingrats[78]
Heliotropiumindicum InaPhaseIstudyconsistingofSolidtumourpatientswhohaveundergonepriorchemotherapy/radiation
therapy,IndicineN-oxide,analkaloidfromHeliotropiumindicumhaveshownsomeimprovementagainst
skinmelanomaandovariancarcinoma[98]
Moringaoleifera Pre-treatmentwiththeleafextractofM.oleiferaexhibitssignificantradiationprotectiontothebonemarrow
chromosomesinmiceandthiscouldbeusefultoovercomesideeffectsofradiationtherapy [99]
Nigellasativa InmicebearingEhrlichascitescarcinoma,thymoquinone(TQ),themainconstituentofthe Nigellasativa
oil,significantlyenhancedthetherapeuticefficacyofifosfamidebyimprovingitsantitumoureffectand
reducingitsnephrotoxicity.Furthermore,micetreatedwithifosfamideincombinationwithTQshowedless
bodyweightlossandmortalityratecomparedtoIFOsingletherapy [100]
Ocimumsanctum OrientinandVicenin,twowater-solubleflavonoidsisolatedfromtheleavesofOcimumsanctumhaveshown
significantprotectiontothehumanlymphocytesagainsttheclastogeniceffectofradiation,radiationlethality
andchromosomalaberrationsinvivo.Thisradioprotectionassociatedwiththeirantioxidantactivitymay
haveclinicalpotentialincancertherapy[101]
Taxusbuccata InaPhaseIIstudy,thetripletregimenbasedontaxol(activeconstituentofTaxusbuccata),ifosfamide,and
carboplatinhasprovedactive,safe,andeasytodeliveronanoutpatientbasisforpatientswithadvanced
stageIIIB-IVnon-small-celllungcancer[102].AnothercombinationofHerceptinwithTaxolsignificantly
improvestheoverallresponserate,increasesthetimetoprogressionandtheoverallsurvivalinbreastcancer
patients.TheseeffectsaremorepronouncedinpatientscharacterizedwithHER/2 +++overexpression
[103].Taxolalsoexertsaweakradiosensitisingeffectonbreastandcervicalcarcinomacellsonthebasisof
anoptimalTaxol/radiationscheduling[104]
Withaniasomnifera W.somniferawhenadministeredfor4daysbeforepaclitaxeltreatmentandcontinuedfor12dayscaused
significantreversalofneutropeniaofpaclitaxelinmice.Itcanbeusedasanadjuvantduringcancer
chemotherapyforthepreventionofbonemarrowdepressionassociatedwithanticancerdrugs [105].The
activecomponent,withaferinAisolatedfromtheextractshowedsignificantantitumourandradiosensitising
effectsinexperimentaltumoursinvivo,withoutanynoticeablesystemictoxicity [106].InEhrlichascites
carcinomamice,theextractshoweddosedependentinhibitionontumourgrowthandincreasedthesurvival
rate.Combinationofradiationtherapywithextractincreasedtumourcureandtumour-freesurvival [107].It
alsoreducescyclophosphamideinducedmyelosuppressionandleucopoeniacanbeusefulincombination
chemotherapy[108,109]
racemosa, Vitis vinifera, Plumbago zeylenica, Tinospora antidysenterica, Punica granatum, Cyperus rotundus, Em-
cordifolia,Zingiberofficinale,Coptidisrhizoma,etc.These blica officinalis, and Plumbago zeylanica can be used as
herbs have been shown to improve appetite, food intake, anti-diarrhoeals when diarrhoea becomes one of the com-
malnutrition, fatigue and sensation of well-being which plications of cancer cachexia. Terminalia chebula could be
could elicit bodyweight gain. These herbs might stimulate useful against chronic constipation and digestive disorders
the flow of digestive juices, thereby improving digestion which are common in cancer patients resulting in loss of
and increasing the appetite. Aegle marmelos, Holarrhena appetite. Eclipta prostrata, Emblica officinalis, Withania
26 P.Balachandran,R.Govindarajan/PharmacologicalResearch51(2005)19–30
Table5
PharmacologicaldetailsofAyurvedicanticancerherbs[110–114]
Nameoftheherb Therapeuticdose Safety/duration/toxic Sideeffects/contraindications Interactionswithother
dose herbs/drugs
Abrusprecatorius Leafdecoction: Likelysafe Nausea,stomach Noneknown
56–112ml,rootpowder: cramping,coma,
0.5–1g circulatorycollapse
Alliumsativum 2–5gperday,solid Likelysafe Excesscancause Mayinteractwithaspirin
extract:0.3–1g,oil: stomachupset.May
0.03–0.12mlt.i.d. increasetheriskof
hemorrhagic
complications
Aloevera Extract:10–20ml, Safeforshortterm Longtermintakemay Possiblyinteractwith
powder:0.05–0.2g therapy aggravateulcers, cardiacglycosidesand
haemorrhoids diuretics
Alstoniascholaris Liquidextract:4–8ml Insufficientinformation Lethargy,Nasal InteractwithSt.John’s
available congestion,allergy wort,generalanaesthetics
Amorphopallus 0.3–0.6g Likelysafe Nonereported Noneknown
campanulatus
Anacardiumoccidentale Notypicaldosage Safe Nonereported Noneknown
Andrographispaniculata Powder:1.5–6g,juiceof Safe Nausea,anorexia, Interactwith
leavesandstem:1–4ml emesis,Urticaria anticoagulantand
t.i.d.,andrographolide: antihypertensive
4–6mg drugs/herbs
Asparagusracemosa Powder:20–30g Safe Noadverseeffects Noneknown
Bacopamonniera 5–10g(0.4–0.5g8×) Safe Rarelycausedermatitis Noneknown
perday
Berberisaristata Powder:1–3g Maybetoxicathigher Maycauselethargy,nose Mayinterferewith
dosage bleeds,nausea,vomiting, VitaminBassimilation
diarrhoea
Boswelliaserrata 0.4g/2–3timesaday, Safe Noadverseeffects Noneknown
gumresin:2–3g,oil: reported
1–1.5ml,barkdecoction:
56–112ml
Calotropiscylindric 0.5–1g Likelyunsafe Vomiting,diarrhoea, Mayinteractwith
bradycadia cardioactiveherbsand
horsetail
Curcumalonga 1.5–3.0g Safe,non-toxic Contraindicatedin Nointeractionsreported
gastriculcers
Daturastramonium 0.05–0.1g Likelyunsafe Vomiting,hypertension, Mayinteractwith
lossofconsciousness. anti-cholinergicdrugs
Mayleadtocoma
Erythrinasuberosa 28–32g Insufficientinformation Insufficientinformation Insufficientinformation
available available available
Euphorbiahirta Powder:0.12–0.3g, Noinformationabout Nausea,vomiting, Nointeractionsknownto
liquidextract:0.1–0.3ml safety.Tolerabledose:up dermatitiswithskin occur
to1g/i.p.inmice contact
Ficusreligiosa Powderedbark:1–3g, Likelysafeatgiven Largeamountscancause Nonereported
liquidextract:60–120ml dosage catharsis/allergies
Gynandropispentaphylla 2g Insufficientinformation Insufficientinformation Insufficientinformation
available available available
Hygrophilaspinosa Seedpowder:2–8g, Insufficientinformation Insufficientinformation Insufficientinformation
liquidextract:40–50ml available available available
Ixoracrocinea 2–2.5g Insufficientinformation Insufficientinformation Insufficientinformation
available available available
Juniperuscommunis 2–10gperday Limittomaximumof6 Longtermmaycause Possiblyinteractwith
weeksLikelysafefor kidneydamage anti-diureticdrugs
shortterm
Luffacylindrica 1.3–1.9g Likelysafe Nonereported Nointeractionsknownto
occur
Meliaazedarach Liquidextract:15–30ml Insufficientinformation Insufficientinformation Insufficientinformation
available available available
Neriumindicum 0.25–0.4g Likelyunsafe Nausea,vomiting, Noneknown
diarrhoea
Nigellasativa 1–3g Safe Noadverseeffects Nointeractionsknown
reported
P.Balachandran,R.Govindarajan/PharmacologicalResearch51(2005)19–30 27
Table5(Continued)
Nameoftheherb Therapeuticdose Safety/duration/toxic Sideeffects/contraindications Interactionswithother
dose herbs/drugs
Ocimumsanctum 1–3g,leafinfusion: Likelysafe Maycauseconstipation Noneknown
4–12ml athigherdosageforlong
term
Paederiafoetida 2–4g,infusion:12–24ml, Non-toxicupto2g/kgin Insufficientinformation Insufficientinformation
liquidextract:56–112ml ratsandmice available available
Phyllanthusniruri Powder:3–6g Safe Nonereported Nonereported
Picrorrhizakurroa 0.5–1g Lowpotentialfortoxicity Nausea,diarrhoea,skin Noneknown
rashathighdoses,
contraindicationsin
pregnancy
Piperlongum 0.5–1g Likelysafe Mayhavecontraceptive Piperinemayinteract
activity,avoiduseduring withenzymaticdrug
pregnancyandlactation biotransformation
Plumbagozeylanica 1–2g PlumbaginLD50 Nonereported Noneknown
10mg/kginmice,whole
plant:0.5g/kg/i.p.
Raphanussativus 15–23g,liquidextract: Likelysafe Largeamountsmay Nointeractionsknownto
50–100ml causeirritationofGI occur
mucusmembrane
Rubiacordifolia Powder:1–3g,liquid Generallyrecognizedas Noadverseeffects Noneknown
extract:56–112ml safe reported
Semecarpusanacardium Oil:1–2drops,fruit: Likelyunsafe Anacardicacidmaybe Nosufficientinformation
0.5–1.5g allergenic available
Taxusbuccata Dosagedependson Likelyunsafe Vomiting,abdominal Nointeractionsknownto
severityofthedisease pain,dyspnea occur
Tinosporacordifolia Powder:1–3g,liquid Safe Nausea Excessivedosemight
extract:56–112ml inhibitVitaminB
assimilation
Vincarosea Dosagedependson Likelyunsafe GIupset,hepatotoxicity, Nointeractionsknownto
severityofthedisease nausea,vomiting,may occur
alsocausehypoglycemia
Vitisvinifera 0.15–0.3g Safe Nonereported Noneknown
Withaniasomnifera 2–6g Likelyunsafe Nausea,dermatitis, Maypotentiatetheaction
abdominalpain,diarrhoea ofbarbituratesand
benzodiazepines
somnifera, Piper longum can be directed to correct nau- andshortnessofbreatheespeciallyforlungcancerpatients
sea and vomiting [60]. Among the above-mentioned herbs, [60]. Thus, ayurvedic therapeutic regimen rejuvenates the
Withania somnifera [61] and Tinospora cordifolia [42] are body tissues, tones up the systems and act as a tonic to
alsoproventobepowerfulimmunostimulants,whichcould the body against cancer cachexia. This kind of orientation
increase body resistance power during cancer associated towardtotalhealingandhealthpromotionmakesayurvedic
immunosuppression. treatmentapproachtocancertherapypromising.
Ayurvedic anticancer therapy includes recommendations
for lifestyle and use of specific foods and herbs which are
very helpful not only in preventing the progression of the 4. Cancer therapy in Ayurveda—learning from the
disease but also makes the patients feel better and com- past,examiningthepresentandadvancingtothefuture
fortable overcoming the symptoms. Allium sativum (garlic)
couldbehelpfultomanagepainandache.Bacopamonniera Because large population use ayurvedic medicine world-
strengthens mental faculties and helps to manage insomnia wide, there is an urgent need for additional, carefully
or sleeplessness due to stress [62]. An herbal combination conducted, high-quality intensive research to evaluate its
of Withania sominifera, Asparagus racemosa, Hydrocotyle efficacy and to develop this discipline to meet ever-new
asiatica, Nardostachys jatamamsi, Elettaria cardamomum, challenges of modern medicine in the field of oncology.
Tribulus terrestris, Zingiber officinalis and Eclipta alba The most stringent evaluation should take place with gold
could also be useful in the treatment of anxiety, tension standards for clinical research—the randomised controlled
and insomnia. Ocimum sanctum is beneficial against stress clinical trial (RCT). Priority for research funding should
anddepressionduringcancer.Curcumalonga,Zingiberof- be given to clinical investigations in Ayurveda involving
ficinale, Glycyrrhiza glabra, Terminalia chebula, Ocimum well-designed studies with encouraging results especially
sanctum and Adhatoda vasica are used to control cough for diseases like cancer to which conventional medicine
28 P.Balachandran,R.Govindarajan/PharmacologicalResearch51(2005)19–30
has been shown to be less effective. Attention should be [10]PandeyG.AnticancerherbaldrugsofIndiawithspecialreference
given not only to the evaluation of safety and examination toAyurveda.NewDelhi:SriSatguruPublications;2002:18–121.
[11]Sharma PV. Charaka samhita. Varanasi: Choukhamba Orientalia;
of effectiveness in treatment strategy, but also to the con-
1981.
sideration of community practice settings, patient expecta-
[12]BhishagrathaKL.Sushrutasamhita.Varanasi:ChoukhambaOrien-
tions, compliance and cost effectiveness. Standardization
talia;1991.
and quality production of herbal products may allow us to [13]Prasad GC. Studies on cancer in Ayurveda and its management.
develop low cost therapies with reduced risk over pharma- JRAS1987;3:147–67.
ceuticals.Inanycase,studiesonanticancerayurvedicdrugs [14]SinghRM.Anassessmentofayurvedicconceptofcancerandanew
paradigmofanticancertreatmentinAyurveda.JAlternComplement
will be popular from the economy point of view because
Med2002;8:609–14.
cancerisbecomingthemajorcauseofdeath.
[15]Sankaran PS. Swellings. In: Prasad GC, Udupa KN, editors.
Susruta’scontributiontosurgery.Varanasi:IndologicalBookHouse;
1976.p.99–111.
5. Conclusionandfuturedirections [16]Dash B, Kashyap L. Diagnosis and treatment of Galaganda, Gan-
damala, Apaci, granthi and arbuda. In: Dash B, Kashyap L, edi-
tors.Diagnosisandtreatmentofdiseasesinayurveda.NewDelhi:
The clinical efficacy and extent of toxicity of numerous
ConceptPublishingCompany;1987.p.437–66.
anticanceragentsareunknownanduncertain.Forexample, [17]SastryJLN.Introductiontooncology,cancerinAyurveda.Varanasi:
researchonmajorityofayurvedicdrugsisinthepre-clinical Chaukhambhaorientalia;2001.p.1–24.
phase or is not being actively pursued. Future research on [18]Thatte U, Dhahanukar S. Ayurveda, the natural alternative. Sci
Today1991;2001:12–8.
this topic would help to identify safe and effective anti-
[19]RamA.Astanga-hrdayaofvagbhata.vol.III.Uttara-sthana.Delhi:
cancerdrugsandwillfurthertheexplorationoftheirmech-
UppalPublishingHouse;1999.
anism of action. Ayurvedic practitioners and researchers in
[20]KinjavadekaraRS.Astangasangraha.NewDelhi:UppalPublishing
medical sciences can help to improve this medicine by in- House;1998.
creasing their involvement and contribution. Case study is [21]Sharma PV. Chakradatta: a treatise on principles and practices of
the research design, which can form basis for future re- Ayurvedicmedicine.NewDelhi:VedamsBooksInternational;1998.
[22]MurthyKRS.Sarangadharasamhita.Varanasi:ChaukambhaOrien-
search directions and can provide valuable contributions to
talia;1987.
the medical field with minimal cost budgets. Case studies
[23]Murthy KRS. Bhavaprakasa of bhavamisra. vol. II. Madhya and
have also been suggested by the NCCAM (National Cen- UttaraKhanda.Varanasi:KrishnadasAcademy;2001.
terforComplementaryandAlternativeMedicine,Bethesda, [24]Sonata S. The efficacy of Ayurveda drugs on Cancer (Arbuda).
USA) as a means to determine whether a complementary Workshoponcancersouvenir.Chennai:CentralResearchInstitute
forSiddha;1986.
anticancer therapy demonstrates potential efficacy against
[25]TreadwayS.AnAyurvedicherbalapproachtoahealthyliver.Clin
particular cancer and whether clinical development of the
NutrInsights1998;6:1–3.
therapy should continue [63,64]. It is no longer an option
[26]Trivedi N, Rawal UM. Effect of aqueous extract of Andrographis
to ignore ayurvedic drugs or treat them as something un- paniculataonlivertumour.IndianJPharmacol1998;30:318–22.
conventionalfromregularmedicalpractices.Thechallenge [27]TrivediNP,RawalUM.Hepatoprotectiveandantioxidantproperty
putbeforethismedicineistomoveforwardcarefully,using ofAndrographispaniculatainBHCinducedliverdamageinmice.
IndianJExpBiol2001;39:41–6.
bothreasoningandwisdom.
[28]Singh RP, Bannerjee S, Rao AR. Modulatory influence of An-
drographis paniculata on mouse hepatic and extrahepatic carcino-
gen metabolising enzymes and antioxidant status. Phytother Res
2001;15:382–90.
References
[29]KapilA.Antihepatoxiceffectsofmajorditerpenoidconstituentsof
Andrographispaniculata.BiochemPharmacol1993;46:182–5.
[1]Hartwell JL. Plants used against cancer. A survey. Lloydia [30]ChihH,ChiuHF,TangKS,ChangFR,WuYC.Bullatacin,apotent
1969;32:247–96. antitumourannonaceousacetogenin,inhibitsproliferationofhuman
[2]Hartwell JL. Plants used against cancer. A survey. Lloydia hepatocarcinoma cell line 2.2.15 by apoptosis induction. Life Sci
1969;32:153–205. 2001;69:1321–31.
[3]Hartwell JL. Plants used against cancer. A survey. Lloydia [31]ChangFR,WuYC.Novelcytotoxicannonaceousacetogeninsfrom
1969;32:78–107. Annonamuricata.JNatProd.2001;64:925–31.
[4]Hartwell JL. Plants used against cancer. A survey. Lloydia [32]Rajeshkumar NV, Kuttan R. Phyllanthus amarus extract adminis-
1970;33:288–392. trationincreasesthelifespanofratswithhepatocellularcarcinoma.
[5]Hartwell JL. Plants used against cancer. A survey. Lloydia JEthnopharmacol2000;73:215–9.
1970;33:97–194. [33]Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk RD, Gupta
[6]Hartwell JL. Plants used against cancer. A survey. Lloydia S. Phyllanthus amarus down-regulates hepatitis B virus mRNA
1971;34:386–425. transcriptionandreplication.EurJClinInvest1996;26:1069–76.
[7]Hartwell JL. Plants used against cancer. A survey. Lloydia [34]Koul IB, Kapil A. Evaluation of the liver protective potential of
1971;34:204–55. piperine.PlantaMed1993;59:413–7.
[8]Hartwell JL. Plants used against cancer. A survey. Lloydia [35]CavalliF,TschoppL,GerberA,SonntagRW,RysselHJ,Brunner
1971;34:310–61. KW. Therapiersultate mit VP 16.213 allein oder kombiniert mit
[9]Hartwell JL. Plants used against cancer. A survey. Lloydia 5-fluorouracil beim leberzell karzinom (hepatoma), Schweiz. Med
1971;34:103–50. Wochenschr1977;107:1960–6.