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Research in Plant Biology, 1(3): 01-14, 2011 ISSN : 2231-5101
www.resplantbiol.com
Mini-Review
Natural plant resources in anti-cancer therapy-A review
M. Joyce Nirmala, A. Samundeeswari and P. Deepa Sankar*
School of Bio Sciences and Technology, VIT University, Vellore – 632014, Tamil Nadu, India
*Corresponding Author: E-mail: pdeepasankar@vit.ac.in
Cancer is one of the most common devastating disease affecting millions of people per
year. Cancer has been estimated as the second leading cause of death in humans. So there
has been an intense search on various biological sources to develop a novel anti-cancer drug
to combat this disease. Plants have proved to be an important natural source of anti-cancer
therapy for several years. About 30 plant derived compounds have been isolated so far and
are currently under clinical trials. These anti-cancer compounds have been found to be
clinically active against various types of cancer cells. Further research in this area may lead
to better treatment of cancer.
Key words: anti-cancer, apoptosis, clinical trials, plant derivative.
Importance of plant secondary metabolites
Plant secondary metabolites have
proved to be an excellent reservoir of new
medical compounds. Many anti-cancer
agents have been isolated from various plant
sources like Catharanthus roseus, Podophyllum
species, Taxus brevifolia, Camptotheca
acuminate, Betula alba, Cephalotaxus species,
Erythroxylum pervillei, Curcuma longa,
Ipomoeca batatas, Centaurea schischkinii and
many others. Scientists are still attempting to
explore the bioavailability of anti-cancerous
compounds in unexplored plant species.
Anti-cancerous drugs under clinical trials
There are four major structural
classifications of plant-derived anti-
cancerous compounds viz., Vinca alkaloids,
Epipodophyllotoxin lignans, Taxane
diterpenoids and Camptothecin quinoline
alkaloid derivatives. Different anti-cancer
compounds that have been identified and
reported by scientists have been reviewed
under.
1. Vinca alkaloids
Vinca alkaloids belong to an
important class of anti-cancer drugs. The
mechanism of action of Vinca alkaloids is
that they inhibit the cell proliferation by
affecting the microtubular dynamics during
mitosis, and this causes a characteristic block
during mitosis leading to apoptosis. Certain
semi-synthetic analogues have been
developed to increase the therapeutic index.
Vinblastine (VLB) and Vincristine
(VCR) are the two major naturally occurring
active compounds obtained from the
Madagascar periwinkle, Catharanthus roseus
G. Don. (Apocynaceae). These compounds
reported potential activity against
lymphocytic leukemia in mice. Vinorelbine
(VRLB) and Vindesine (VDS) are the two
semi synthetic analogs obtained from the
active compounds. They showed potential
activity against leukemia’s, lymphomas,
advanced testicular cancer, breast cancer,
lung cancer and Kaposi’s sarcoma when
Joyce Nirmala et al. / Research in Plant Biology, 1(3): 01-14, 2011
2
treated in combination with other
chemotherapeutic drugs (Cragg and
Newman, 2005). Vinflunine, a bifluorinated
derivative of vinorelbine exhibits a superior
anti-tumor activity compared to other vinca
alkaloids. This novel Vinca alkaloid is
currently under Phase II clinical trials. Both
Vinflunine and Vinorelbine exhibits reduced
toxicity in animal models
(Okouneva et al.,
2003; Simeons et al., 2008).
2. Podophyllotoxin
Podophyllotoxin is obtained from the roots of
Podophyllum species, namely, Podophyllum
peltatum Linnaeus and Podophyllum emodi
Wallich. This was isolated in 1880s, and their
structure was elucidated in 1950s.
Epipodophyllotoxin is an isomer of
podophyllotoxin. The two clinically
important semi-synthetic analogs generated
from Epipodophyllotoxin are Etoposide and
Teniposide which were found very potential
in treating lymphomas, bronchial and
testicular cancers
(Shoeb, 2006).
3. Taxanes
Paclitaxel (Taxol
®
) is obtained from the bark
of the Pacific Yew, Taxus brevifolia Nutt.
(Taxaceae). Their structure was first
identified in the year 1971 and they entered
the market since 1990s. Another species,
Taxus baccata, an Indian Ayurvedic medicine
have also been in use for cancer therapy
(Kingston, 2007).
Paclitaxel was found poorly
water-soluble and toxic, hence, a water-
soluble compound, Docetaxel was derived.
Docetaxel (Taxotere
®
), a semi-synthetic
derivative of paclitaxel was found more
effective. Docetaxel can be used in patients
who are resistant to paclitaxel. Both docetaxel
and paclitaxel are used as first- and second-
line treatment in patients suffering from
metastatic cancer, breast cancer and ovarian
cancer. These drugs are also found active
against lung cancer, prostate cancer and also
lymphoid malignancies. The mechanism of
action is that these active agents bind to the
polymerized microtubules which prevent the
normal mitosis to occur and thus they are
called anti-mitotic drugs (Hait et al., 2007).
4. Camptothecin (CPT)
Camptothecin is a cytotoxic alkaloid isolated
mainly from the bark and stem of the
Chinese ornamental tree, Camptotheca
acuminate. It showed poor solubility and
severe toxicity, and, because of this reason,
certain analogues of CPT were synthesized to
overcome these disadvantages. They are
topotecan, irinotecan (CPT-11), 9-
aminocamptothecin (9-AC), lurtotecan and
rubitecan. These analogs work by inhibiting
DNA Topoisomerase I which plays a major
role in various DNA functions like
replication and transcription. It is made up of
a pentacyclic ring structure which contains a
pyrrole (3, 4 β) quinoline moiety (Srivastava
et al., 2005). The camptothecin molecule has
an S-configured lactone form and a
carboxylate form which is responsible for the
anti-cancer activity.
Topotecan is found clinically effective in
patients with epithelial ovarian cancer and
small cell lung cancer as a second-line
treatment (Creemers et al., 1996). Irinotecan
acts as first- and second-line treatment for
metastatic colorectal cancer (Fuchs et al.,
2006). DX-8951f (Exatecan) is yet another new
camptothecin (CPT) derivative which
demonstrated potential anti-tumor activity
against various tumors both in-vitro and in-
vivo (Mineko et al., 2000). This synthetic
analog seems to have better aqueous
solubility, tumor efficiency and lesser toxic
effects compared to camptothecin and other
derivatives (Reichardt et al., 2007). SN-38 (7-
ethyl-10-hydroxycamptothecin), an active
metabolite of CPT-11 is found to show high
cytotoxic activity as compared to CPT-11.
Due to the poor solubility of this
topoisomerase I inhibitor, it is now designed
as a liposome-based formulation. This LE-
Joyce Nirmala et al. / Research in Plant Biology, 1(3): 01-14, 2011
3
SN-38 shows increased cytotoxic effects in
various cancer cell lines (Zhang et al., 2004).
CZ-48 acts as effective anti-cancer agent, with
not much toxicity effects in mice. Research is
still undergoing for human clinical trials also
(Cao et al., 2009).
5. Berbamine
Berbamine, a bisbenzylisoquinoline alkaloid
was isolated from the Chinese herb named
Berberis amurensis. It was reported that
Gleevec was responsible for bcr/abl tyrosine
kinase inhibition and therefore used in the
treatment of chronic myeloid leukemia. But
few patients developed resistance against
this drug. It was found that berbamine
effectively causes cell apoptosis of both
Gleevec sensitive and resistant Ph
+
chronic
myeloid leukemia cells. They work by
inducing caspase-3-dependent apoptosis of
leukemic NB4 cells by the survivin-mediated
pathway (Xie et al., 2009; Xu et al. 2006).
6. Berberine
Berberine, an isoquinoline plant alkaloid is
obtained from different plant species
including Hvdrastis Canadensis L.,
(Ranuncufaceae), Berberineeris species
(Berberidaceae) and Arcungelisia flaw
(Menispermaceae). They showed anti-tumor
activity both in-vivo and in-vitro report show
that berberine has found effective against
osteosarcoma, lung, liver, prostate and breast
cancer (Wang et al., 2011; Patil et al., 2010).
7. Beta-lapachone
Beta-lapachone (3, 4-dihydro-2, 2-dimethyl-
2H-naphthol [1, 2-b] pyran-5, 6-dione), a
water-insoluble orthonapthoquinone
compound, was obtained from the
heartwood of South American Lapacho tree
(Tabebuia avellanedae)
(Li et al., 2000). This
compound has a broad spectrum of
antineoplastic activity against breast cancer,
prostate cancer, lung cancer, pancreatic
cancer and also in promyelocytic leukemic
cells. They work by inhibiting Topoisomerase
I and II (De Almeida, 2009). But this drug is
found to have poor solubility, systemic
toxicity and non-specific distribution. So,
gold nanoparticles are being used as a carrier
in delivering the drug in the nano form to
enhance the radiotherapeutic efficiency
(Jeong et al., 2009).
8. Betulinic acid
Betulinic acid (3β, hydroxy-lup-20(29)-en-28-
oic acid), a lupine class type, pentacyclic
triterpene compound is obtained naturally
from various plant species. This compound is
obtained in good amounts from the bark of
many trees, including white-barked birch
trees (Betula alba). The mechanism of action of
betulinic acid is that they trigger the
mitochondrial pathway of apoptosis which
causes cancer cell death. Thus this compound
exhibits potent anti-cancer activity in humans
(Fulda, 2008).
9. Bruceatin
Bruceantin, a plant derivative exhibits anti-
tumor activity. This anti-tumor compound
work by irreversible inhibition of protein
synthesis in HeLa cells, rabbit reticulocytes,
and reticulocyte lysates. It is seen that
bruceantin exhibits secondary effect on the
synthesis of DNA (Liaoo et al., 1976).
10. Colchicine
Colchicine is a plant secondary metabolite
extracted from Colchicum autumnale and
Gloriosa superba L. It causes mitotic arrest
during cell cycle and thus they are
considered as potent anti-mitotic drug both
in-vitro and in-vivo. Due to severe toxic
effects, certain derivatives of colchicine were
synthesized namely, 3-demethyl colchicine,
colchicoside, thiocolchicocide which showed
improved activity against certain leukemic
cells and solid tumors. Research is still
undergone in the area of anti-cancer therapy
(Dubey et al., 2008).
Joyce Nirmala et al. / Research in Plant Biology, 1(3): 01-14, 2011
4
11. Combretastatin A-4
Combretastatin A-4 is a naturally occurring
stilbene compound obtained from the South
African bush willow tree, Combretum caffrum
Kuntze. This vascular targeting agent
disrupts the tubulin structure and the change
in morphology of endothelial cells causes
deprivation of nutrients to tumor cells by
impeding the blood flow through capillaries.
Due to its poor solubility, a water-soluble
prodrug called Combretastatin A-4 disodium
phosphate has been formulated for
experimental purpose which is currently
under phase II clinical trials (Thomson et al.,
2006; Ley et al., 2007).
12. Cucurbitacin
Cucurbitacin, a tetracyclic triterpenoid
compound is predominantly obtained from
the Cucurbitaceae plants. They possess
antiproliferative behavior against various
cancer cell lines. Reports show that
Cucurbitacin- I and B selectively inhibit both
signal transducer/Janus Kinase 2 (JAK2)
activity and activator of transcription 3
(STAT3) pathways. STAT3 is activated in
many cancer cell types like prostate cancer,
breast cancer and also carcinoma of the head,
neck and nasopharynx. Reports show that
inhibition of this oncogenic signaling
pathway, STAT3, causes tumor cell growth
inhibition and leads to apoptosis of cancer
cells. Polymeric miscelles are used in
delivering this compound because of its
water insolubility and non-specific toxicity
(Molavi et al., 2008; Bernard and Olayinka et
al., 2010).
13. Curcumin
Curcumin (diferuloylmethane), a
polyphenolic compound is isolated from the
Indian plant spices, Curcuma longa
(commonly called turmeric), now finds its
application as potential anti-cancer
compound. About 3–5% of this yellow
pigment of turmeric contains curcuminoids.
Curcumin is involved in modulating the cell
cycle pathway and induces apoptosis of
various cancer cells. But the exact mechanism
of action is yet to be studied clearly. Phase
I/II trials are ongoing on the effects of
curcumin on colorectal cancer, multiple
myeloma and pancreatic cancer. Curcumin
used at a high dosage level is reported to be
safe by phase I clinical trials (Sa et al., 2010;
Goel et al., 2008).
14. Daphnoretin
Daphnoretin, a bis-coumarin derivative,
extracted in good amounts from the root bark
of Wikstroemia indica (Thymelaeaceae) was
found to have good anti-cancer activity (Lu et
al., 2011). Daphnoretin causes suppression of
protein and DNA synthesis in Ehrlich ascites
carcinomas. It is also seen to suppress the
hepatitis B surface antigen expression on
human hepatoma Hep3B cells (Diogo et al.,
2009).
15. Diadzein and Genistein
Diadzein (4', 7- Dihydroxyisoflavone) and
Genistein (4', 5, 7-Trihydroxyisoflavone) are
the two aglycones present abundantly in the
Soy Isoflavones. Major sources include
important legumes like lupine (Lupinus
spp.), fava bean, (Vicia faba), soybeans
(Glycine max), kudzu (Pueraria lobata), and
psoralea (Psoralea corylifolia) (Kaufman et
al., 1997). These phytochemicals work by
inhibiting 3A4-mediated metabolism.
Reports show that they are capable of
inhibiting oxidative metabolism also (Moon
et al., 2006). Genistein is found to inhibit cell
proliferation in both ovarian and breast
cancers. They also inhibit chemically induced
cancers in stomach, bladder, lung, prostate,
colon and blood
(Dixon and Ferreira et al.,
2002).
16. Ellipticine
A plant alkaloid, Ellipticine (5, 11-dimethyl-
6H-pyrido [4, 3-b] carbazole) and its
derivatives were isolated from Apocynaceae
Joyce Nirmala et al. / Research in Plant Biology, 1(3): 01-14, 2011
5
plant species (eg. Ochrosia borbonica, Excavatia
coccinea, Ochrosia elliptica). They exhibit
significant anti-tumor properties against
various cancer cell types. The primary
function of this drug is that it intercalates
with DNA and also causes inhibition of
Topoisomerase II activity. It is also reported
that this drug, inhibits cell growth and causes
apoptosis of human hepatocellular carcinoma
HepG2 cells (Kao et al., 2006).
Table 1. List of plant derivatives used in cancer therapy
S.
No
Semisynthetic
analogs of
plant
derivatives
Species and
Genus name
Experiments on various
cancer cells
Mechanism of action Reference
1 Vindesine and
Vinorelbine
Catharanthus
roseus
Leukemias, lymphomas,
advanced testicular cancer,
breast cancer, lung cancer
and Kaposi’s sarcoma.
mitotic block Cragg and
Newman, 2005
2 Vinflunine
Catharanthus
roseus
Reduced toxicity in animal
models
mitotic block Okouneva et al.,
2003; Simeons et
al., 2008
3 Etoposide and
Teniposide
Podophyllum
peltatum and
Podophyllum
emodi
Lymphomas, bronchial
and testicular cancers.
- Shoeb, 2006
4 Taxol
®
Taxus brevifolia
Nutt, Taxus
baccata
Metastatic, breast, ovarian,
lung, prostate cancer and
lymphoid malignancies
Anti-mitotic Kingston, 2007
5 Taxotere
®
Taxus brevifolia
Nutt, Taxus
baccata
Used in patients resistant
to Paclitaxel
Anti-mitotic Hait et al., 2007
6 Topotecan
Camptotheca
acuminate
Epithelial ovarian cancer
and small cell lung cancer
DNA topoisomerase I
inhibition
Creemers et al.,
1996
7 Irinotecan
Camptotheca
acuminate
Metastatic and colorectal
cancer
DNA topoisomerase I
inhibition
Fuchs et al., 2006
8 Exatecan
Camptotheca
acuminate
Potential anti-tumor
activity both in vitro and in
vivo
DNA topoisomerase I
inhibition
Mineko et al.,
2000
9 LE-SN-38
Camptotheca
acuminate
Various cancer cell lines DNA topoisomerase I
inhibition
Zhang et al., 2004
10 Berbamine
Berberis
amarensis
Chronic myeloid leukemia Caspase-3-dependent
apoptosis
Xie et al., 2009; Xu
et al., 2006
11 Berberine
Hvdrastis
canadensis L.,
Berberineeris sp&
Arcungelisia flaw
Osteosarcoma, lung, liver,
prostate and breast cancer
Not known Wang et al., 2011;
Patil et al., 2010
12 Beta-
lapachone
Tabebuia
avellanedae
breast cancer, prostate
cancer, lung cancer,
pancreatic cancer and
promyelocytic leukemia.
Inhibition of
topoisomerase I and
II
Li et al., 2000; De
Almeida, 2009
Joyce Nirmala et al. / Research in Plant Biology, 1(3): 01-14, 2011
6
13 Betulinic acid
Betula alba
Exhibits anti-cancer
activity in humans
Triggers
mitochondrial
pathway of apoptosis
Fulda, 2008
14 Colchicine
Colchicum
autumnale and
Gloriosa superba
L.
Leukemic and solid tumors Anti-mitotic Dubey et al., 2008
15 Combretastati
n A-4
Combretum
caffrum Kuntze
Phase II clinical trials Tubulin structure
disruption
Thomson et al.,
2006; Ley et al.,
2007
16 Cucurbitacin Cucurbitaceae
species
Various cancer cell lines Inhibits signal
transducer/JAK 2
activity and activates
STAT3 pathway
Molavi et al.,
2008; Bernard and
Olayinka et al.,
2010
17 Curcumin
Curcuma longa
colorectal cancer, multiple
myeloma and pancreatic
cancer.
Exact mechanism of
action is still
unknown
Sa et al., 2010;
Goel et al., 2008
18 Daphnoretin
Wikstroemia
indica
a) Ehrlich ascites
carcinomas and
b) human hepatoma
Hep3B cells.
a) suppression of
protein and DNA
synthesis
b) suppresses
Hepatitis B surface
antigen expression
Lu et al. 2011;
Diogo et al., 2009
19 Diadzein and
Genistein
Lupinus species,
Vicia faba,
Glycine max,
Psoralea
corylifolia
Genistein inhibits ovarian
and breast cancers and also
chemically induced cancers
of stomach, bladder, lung,
prostate, colon and blood.
Inhibits 3A 4-
mediated metabolism
and oxidative
metabolism
Kaufman et al.,
1997; Moon et al.,
2006; Dixon and
Ferreira et al.,
2002
20 Ellipticine
Ochrosia
borbonica,
Excavatia
coccinea,
Ochrosia elliptica
Various cancer cell types DNA intercalation
and inhibition of
topoisomerase II
Kao et al., 2006
21 Emodin Rhizome of
rhubarb
lung, liver, ovarian and
blood cancer
Apoptosis of cancer
cells by several
pathways
Huang et al., 2009
22 Flavopiridol
Amoora rohituka
and Dysoxylum
binectariferum
colorectal, non-small cell
lung cancer, renal cell
carcinoma, non-Hodgkin’s
lymphoma, chronic
lymphocytic leukemia, and
also solid tumors
Inhibits cell cycle
progression at G1 or
G2 phase
Mans et al., 2000
23 Harringtonine
and
Homoharring-
tonine
Cephalotaxus
harrintonia, C.
hainanensis and
C. qinensis
Acute myeloid leukemia
and chronic myeloid
leukemia.
Inhibition of protein
synthesis and chain
elongation during
translation
Cragg and
Newman, 2005;
Efferth et al., 2007
24 Indirubin Chinese herb,
Danggui
Longhui Wan
Chronic myeloid leukemia Inhibits cyclin-
dependent kinases
Nam et al., 2005
Joyce Nirmala et al. / Research in Plant Biology, 1(3): 01-14, 2011
7
25 Ingenol 3-o-
angelate
Euphorbia peplus
L.
actinic keratosis and basal
cell carcinoma
Causes necrosis of
tumor by the
activation of PKC
Hampson et al.,
2005
26 4-Ipomeanol
Ipomoeca batatas
Lung specific cancer in
animal models
cytochrome P-450-
mediated conversion
into DNA-binding
metabolites
Ancuceanu and
Istudor, 2004
27 Irisquinone
Iridaceaelatea
pallasii and Iris
kumaoensis
Good activity in
transplantable rodent
tumors
Acts as a
chemosensitizer
Hazra et al., 2004
28 Phenoxodiol
plant isoflavone,
genistein
Ovarian, prostate and
cervical cancer
inhibit plasma
membrane electron
transport and cell
proliferation
Herst et al., 2009
29 Pandimex
TM
saponins of
ginseng
Advanced cancers of
breast, colon-rectum, lung,
pancreas and solid tumors
Cell cycle arrest and
acts as P-glycoprotein
blocker
Pan et al., 2010
30 Perillyl alcohol Many plant
species like
mints, cherries,
lavenders and
many others
Non small cell lung cancer,
prostate cancer, colon
cancer and breast cancer.
Exact mechanism is
yet to be identified
Pan et al., 2010;
Bardona et al.,
2002; Yeruva et
al., 2007
31 Pervilleines
Erythroxylum
pervillei
Yet to be done Inhibitors of P-
glycoprotein
Mi et al., 2001; Mi
et al., 2002; Mi et
al., 2003
32 Salvicine
Salvia prionitis
Hance
Malignant tumors Inhibition of
topoisomerase II
Deng et al., 2011
33 Schischkinnin
Centaurea
schischkinii
Colon cancer lines in vitro
Not known Shoeb et al., 2005
34 Montamine
Centaurea
Montana
CaCo
2
colon cancer cell
line in vitro
Not known Shoeb et al., 2006
35 Silvestrol
Aglaia foveolata
Panell
Prostate, breast and lung
cancers.
apoptosome/mitocho
ndrial pathway was
involved in triggering
extrinsic pathway of
programmed cell
death of tumor cells
Kinghom et al.,
2009; Kim et al.,
2007
36 PG490-88
Tripterygium
wilfordii Hook F
Prostate cancer Enhances the anti-
tumor effects of
cytotoxic and
chemotherapeutic
agents, thereby
induces apoptosis.
Liu, 2011
17. Emodin
Emodin (1, 3, 8-trihydroxy-6-methyl-
anthraquinone) is one of the active
component isolated from the rhizome of
rhubarb. Rhubarb is used as a traditional
Chinese medicine for treating various
Joyce Nirmala et al. / Research in Plant Biology, 1(3): 01-14, 2011
8
diseases. This anthraquinone compound
causes apoptosis in many types of cancers
including lung cancer, liver cancer, ovarian
cancer and blood cancer by several pathways
(Huang et al., 2009).
18. Flavopiridol
Flavopiridol, a semisynthetic flavone
derivative of the plant alkaloid rohitukine is
isolated from the leaves and stems of Amoora
rohituka and also from Dysoxylum
binectariferum (Maliaceae). This anti-cancer
agent works by inhibiting cell cycle
progression at G1 or G2 phase by interfering
with the phophorylation activity of cyclin-
dependent kinases. Flavopiridol is under
phase I trials for treating solid tumors and is
also undergoing phase II clinical trials for the
treatment of wide range cancers like
colorectal, non-small cell lung, and renal cell
carcinoma, non-Hodgkin’s lymphoma and
also chronic lymphocytic leukemia (Mans et
al., 2000). It is also found effective against
rhabdoid tumors, a pediatric malignancy
(Smith et al., 2008).
19. Harringtonine and Homoharringtonine
Harringtonine and Homoharringtonine are
the two alkaloid esters of cephalotaxine. They
were originally used as the traditional
Chinese medicine to cure cancer. These
compounds were isolated from the evergreen
coniferous shrubs of Cephalotaxus species,
like C. harrintonia, C. hainanensis and C.
qinensis. Homoharringtonine is found
effective against various leukaemic cells.
They work by inhibiting protein synthesis
and also cause inhibition of chain elongation
during translation. It is found that, a mixture
of harringtonine and homoharringtonine can
be used in treating both acute myeloid
leukemia (AML) and chronic myeloid
leukemia (CML) (Cragg and Newman, 2005;
Efferth et al., 2007).
20. Indirubin and Meisoindigo
Indirubin is an important active compound
of the traditional Chinese herbal medicine,
Danggui Longhui Wan. Indirubin works by
inhibiting cyclin-dependent kinases, which
causes cell cycle arrest and also inhibits the
proliferation of tumor cells. This active agent
was used in the treatment of chronic myeloid
leukemia (Nam et al., 2005). But due to
various disadvantages of indirubin like poor
solubility and absorption, methylisoindigotin
(abbreviated as meisoindigo) has been
derived. Meisoindigo, a second generation
derivative of indirubin, showed good
efficiency with lower toxicity effects. Their
mode of action is still not fully understood.
Yet it has been reported that they cause
inhibition of DNA and RNA biosynthesis in
W256 cells and also inhibits the microtubular
assembly. This anti-cancer agent is clinically
effective against chronic myeloid leukemia
(CML) (Liu et al., 1996).
21. Ingenol 3-o-angelate
Ingenol 3-angelate (PEP-005), a derivative of
ingenol was originally obtained from the
plant species, Euphorbia peplus L. This
diterpene ester initially causes necrosis of
tumor cells by the activation of PKC leading
to tumor cell death. This compound is under
phase II clinical trials for treating actinic
keratosis and basal cell carcinoma (Hampson
et al., 2005).
22. 4-Ipomeanol
4-Ipomeanol is a pneumotoxic furan
derivative. It is obtained from the sweet
potato Ipomoeca batatas (Convolvulaceae)
which has been affected by Fusarium solani.
The mechanism of action is that it causes
cytochrome P-450-mediated conversion into
DNA-binding metabolites. This
monoterpene, cytotoxic agent showed
promising result for lung-specific cancer in
pre-clinical studies with animal models. But,
unexpectedly, poor results were obtained in a
Joyce Nirmala et al. / Research in Plant Biology, 1(3): 01-14, 2011
9
clinical setting (Ancuceanu and Istudor,
2004).
23. Irisquinone
Irisquinone, a benzoquinone with anti-tumor
activity is obtained from plant species like
Iridaceaelatea pallasii and Iris kumaoensis
(Iridaceae). Irisquinone showed good activity
against transplantable rodent tumors and
also acts as a chemosensitizer (Hazra et al.,
2004).
24. Phenoxodiol and Protopanaxadiol
Phenoxodiol (2H-1-benzopyran-7-0, 1, 3-[4-
hydroxyphenyl], PXD) is a synthetic analog
of naturally occurring plant isoflavone,
genistein. Reports of phenoxodiol
demonstrated that they inhibit plasma
membrane electron transport and cell
proliferation and leads to apoptosis of many
cancer cell lines. This anti-cancer drug is
being developed as a “chemosensitizer” and
is currently under Phase III clinical trials for
treating ovarian cancer and also in the initial
stages of clinical trial for treating prostate
and cervical cancer (Herst et al., 2009).
Protopanaxadiol (Pandimex™) is a triterpene
aglycone obtained from saponins of ginseng.
This compound arrests cell cycle through
various signaling mechanisms leading to
cancer cell death. Protopanaxadiol, an
efficient P-glycoprotein blocker, shows
cytotoxicity against multi-drug resistant
tumors. It is used in treating advanced
cancers of breast, colon-rectum, lung and
pancreas. Protopanaxadiol is under Phase I
clinical trial for the treatment of lung cancer
and solid tumors (Pan et al., 2010).
25. Perillyl alcohol
Perillyl alcohol, a monocyclic monoterpene is
found naturally in many plant species like
mints, cherries, lavenders, lemongrass, sage,
cranberries, perilla, wild bergamot, ginger
grass, savin, caraway and celery seeds.
Perillyl alcohol induces apoptosis,
differentiation and cell cycle arrest in the G
1
phase and causes inhibition of cancerous cell
growth. But the exact mechanism of action is
yet to be identified. Investigation is still being
done on the effectiveness of
chemotherapeutic activity against human
cancers like non small cell lung cancer,
prostate cancer and colon cancer.
Combination therapies were used in treating
breast cancer cells (Pan et al., 2010; Bardona
et al., 2002; Yeruva et al., 2007).
26. Pervilleines
Pervilleines A, B, C, and F are obtained from
the roots of Erythroxylum pervillei. They act as
good inhibitors of P-glycoprotein which
causes a multidrug resistance related to low
response for cancer therapy. Further
investigation on clinical trials is yet to be
done (Mi et al., 2001; Mi et al., 2002; Mi et al.,
2003).
27. Salvicine
Salvicine, a diterpenoid quinone is obtained
as a derivative of the naturally occurring lead
saprorthoquinone compound. This lead
product is isolated from a Chinese medicinal
plant species, Salvia prionitis Hance
(Labiatae). Salvicine reported significant in-
vitro and in-vivo activity against malignant
tumors by inhibiting the activity of
Topoisomerase II (Deng et al., 2011).
28. Schischkinnin and Montamine
Schischkinnin, an indole alkaloid is obtained
from the seeds of Centaurea schischkinii. They
showed moderate in-vitro anti-cancer
activity. Certain flavanoids and lignans were
also isolated from C. schischkinii which
exhibited low cytotoxicity. Most of these
compounds are found effective against colon
cancer cell lines in-vitro (Shoeb et al., 2005).
Montamine, a dimeric indole alkaloid is
obtained from the seeds of Centaurea Montana
(Asteraceae). Among various compounds
isolated from C. Montana, montamine
demonstrated significant in-vitro anti-cancer
Joyce Nirmala et al. / Research in Plant Biology, 1(3): 01-14, 2011
10
potential against CaCo
2
colon cancer cells
(Shoeb et al., 2006).
29. Silvestrol
Silvestrol, a cytotoxic rocaglate derivative is
obtained from the fruits and twigs of Aglaia
foveolata Pannell (Meliaceae). They are found
effective against prostrate, breast and lung
cancers. The mechanism of action of
silvestrol on LNCaP, hormone-dependent
human prostate cancer cell line was studied.
It revealed that an apoptosome /
mitochondrial pathway was involved which
triggers extrinsic pathway of programmed
cell death of tumor cells. Another derivative,
Episilvestrol, an epimer of silvestrol, was
found less effective as a cytotoxic agent when
compared to silvestrol (Kinghom et al., 2009;
Kim et al., 2007).
30. Triptolide
Triptolide is a traditional Chinese medicine
obtained as a purified extract from a shrub-
like vine named Tripterygium wilfordii Hook
F. This diterpenoid triepoxide enhances the
anti-tumor effects of cytotoxic and
chemotherapeutic agents and thereby
induces apoptosis of tumor cells. Because of
its severe toxicity and water insolubility, new
triptolide derivatives like PG490-88 or F60008
have been synthesized which are water-
soluble and proved to be very safe and
effective. PG490-88 (14-succinyl triptolide
sodium salt) is under Phase I clinical trial for
treatment of prostate cancer (Liu, 2011).
The semi-synthetic analogs of plant
derivatives reported by various scientists
have been compiled and given in Table I.
Conclusion
From the preceding review, it can be
concluded that Etoposide and Teniposide are
active against lymphomas, bronchial and
testicular cancer; Topotecan was found active
against epithelial ovarian cancer and small
cell lung cancer; Irinotecan was found
effective against metastatic colorectal cancer;
Homoharringtonine showed potential
activity against various leukemic cells;
Ingenol 3-o-angelate was active against
actinic keratosis and basal cell carcinoma;
PG-490-88 was found active against prostate
cancer; Meisoindigo was effective in patients
with chronic myeloid leukemia; Berberine
was active against osteocarcoma, lung, liver,
prostate and breast cancer; Phenoxodiol was
found active against ovarian cancer.
Protopanaxadiol (Pandimex
TM
) was effective
in treating advanced cancer of the breast,
colo-rectal, lung and pancreatic cancer.
Paclitaxel (Taxol
®
) and docetaxel (Taxotere
®
)
was considered to be the most efficient drug
introduced in the last decade which was
found active against broad spectrum of
cancer cells. Hence there is hope in the
pharmaceutical industry, that even more
powerful commercial drugs can be
developed sooner, using plant derivatives, to
effectively treat cancer and save mankind.
Acknowledgement
The authors are thankful to the management
of VIT University for providing the necessary
support.
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