This document discusses plant-derived anticancer agents that are currently used in clinical practice or show promise as future treatments. It summarizes several prominent plant-derived compounds that are used clinically to treat various cancers, including vincristine, vinblastine, paclitaxel, camptothecin, and podophyllotoxin derivatives. It also outlines some challenges with developing plant-derived anticancer drugs and the process of isolating active compounds from plants and testing their efficacy and safety.

1. Siddhesh S. Bhende
Ad. No. : 2009-12-120
Dept.: Plantation crops and Spices

2. 4-Ipomeanol
O
O
OH
Lapachol
O
OH
O
Bruceantin
O
COCH3HO
O
O
O O
OH
O
HO
H
HH
H
N
N
O
O
O
OH
Camptothecin

3. TUMOUR
A mass of excess tissue that results from abnormal cell
division. Tumors perform no useful body function. They
may be benign (not cancerous) or malignant (cancerous)
.
CANCER
A term for diseases in which abnormal cells divide
without control. Cancer cells can invade nearby tissues a
nd can spread through the bloodstream and lymphatic sy
stem to other parts of the body.

4.  Cancer is a dreadful disease and is the second major cause of
deaths after cardiovascular diseases
 It is a growing public problem whose estimated
worldwide new incidence is about 6 million cases per
year
 The incidence of various forms of cancer is now rapidly
rising world wide
 so combating this disease is of paramount importance to
public health

5. Forms of cancer treatments are
Surgery
Chemotherapy
Immunotherapy
Radiation

6. Impact of chemotherapeutical
agents…
 They are highly reactive and non-
selective
 They cause serious unpleasant side
effects like Nausea , Vomiting , fatigue ,
anemia , taste and smell changes ,
infection , infertility etc

7. A successful anti cancerous drug
should…….
 Kill cancer cells without causing damage
to normal cells
 Plant based therapeutic agents will help
to overcome this problem to some
extent

8. Plant derived anticancer agents inPlant derived anticancer agents in
clinical useclinical use

9. Vincristine & Vinblastine
 First clinically used theraputic drug
 Obtained from: Catharanthus roseus
 Family : Apocyanaceae
 Used for treating a variety of cancers including
leukaemia, lymphomas, advanced testicular cancer,
breast and lung cancer
 Vincristine effective for treating acute childhood
leukemia
 Vinblastine has been especially effective for treating
Hodgkin's disease
1

10. One of the most promising plant-
derived anticancer agents to be
identified in recent years is the taxane-
diterpenoid taxol (paclitaxel)
Clinically introduced into US market in
1990s: isolated from the bark of Pacific
yew tree,Taxus brevifolia (Taxaceae).
: very low yield (0.01-0.03%) –the
bark from 3 trees
is needed to produce 1 gram of taxol!
Paclitaxel ( Taxol )
Taxus brevifolia
2
 Obtained from : Taxus
brevifolia
 Bark
 Active against advanced
breast cancer, ovarian
cancer and lung cancer

11. 3 Camptothecin
 Isolated from : Camptotheca acuminata
 Its synthetic derivatives are topotecan and irinotecan
 Irinotecan: used for treating colo rectal cancer
 Topotecan– used for the treatment of ovarian and
small cell lung cancer

12. Podophyllotoxin≈epiphyllotoxin4
 Isolated from rhizomes of
: Podophyllum peltatum
: Podophyllum emodi
Its semi synthetic derivatives are used in the cancer
treatment .
 Etoposide :cancer, lymphomas and
leukaemias
 Teniposide: paediatric cancer,neuroblastoma
brain tumours

13. Harringtonine and
Homoharringtonine….
 Alkaloid obtained from:
Cephalotaxus harringtonia
var.drupacea
 Used in China : acute leukaemia
 Officinal part: seeds
5

14. Ellipticine and
9-methoxy ellipticine
 Obtained from : Ochrosia elliptica
 Treatment of breast cancer
 They also inhibit broad spectrum
preclinical side-effects like
haemolysis, cardiovascular effect
 Marketed in France
6

15. Combrestatin A-4 (cis-stilbene)
 Combrestatin A-4 (cis-stilbene)
 African bush willow tree
Combretum caffrum
(Combretaceae).
7

17. Folk medicines as potential
anticancer drugs
An alternative solution to allopathic
medicine embodied with severe side effects,
is the use of folk medicine plant
preparations to arrest the insidious nature
of the disease .

18.  Apocynin
 Isolated from Picrorrhiza kurroa (katuka) roots & rhizome
 NADPH oxidase inhibitor
 Has anti-oxidant and anti-inflammatory activity (Basu,
1971).
Picrorrhiza kurroaPicrorrhiza kurroa

19.  Plumbagin
 From Plumbago zeylanica roots
 Has anti cancer activity
 Plumbagin inhibit exponentially growing
tumours
Plumbago rosea & P.zeylanicaPlumbago rosea & P.zeylanica

20. Glycyrrhiza glabraGlycyrrhiza glabra
 Glycyrrhizin
 Obtained from rhizome
 It will inhibit DNA and RNA
synthesis (Badam L. 1994).

21. Butea monospermaButea monosperma
 Famous tree known as - the flame of forest
 Flavone glycoside from leaves
 Inhibited tumour cells in experimental
models (Tirupathi, 2007).

22. Withania somnifera
 Withanolides
 Present in the whole plant.
 They are believed to be immuno modulators having
anticancer activity (Ali M, Shuaib M 1997).

23. New natural products with antitumour activity
*The systematic screening programmes have resulted
in the isolation of many new natural products
exhibiting antitumour activity.
A number of them have been considered sufficiently
active for clinical studies.

24. Tylocrebine
Alkaloid from Tylophora crebiflora (Apocynaceae)
in clinical trial unmanageable CNS effects

25. *Thalicarpine (Thalictrum dasycarpum, Ranunculaceae)
*Tetrandrine (Cyclea peltata, Menispermaceae)
alkaloids clinical trials showed no anti tumour activity
Thalictrum dasycarpum
However tetrandrine was found to
be able to block calcium channel
hence useful in the treatment of CVD

26. Quassinoids or Simaroubolides
Alkaloides isolated from a variety of plants in the
Simaroubaceae family are currently of interest for their
for antitumour properties.
Bruceantin
*alkaloid from Brucea antidysenterica
* used to treat cancer in Ethiopia
*shows high anti leukaemic activity at low dose
*acts through inhibition of protein synthesis

27. Maytansinoids
From Maytenus serrata and other species of Maytenus,
mosses and Actinomycete
Maytenus ilicifolia
(Celastraceae)
*Active against several neoplasms at
*Mitotic inhibitor

28. •From Tripterygium wilfordii (Celastraceae)
•potent anti leukaemic agents contains only small
amounts
• In China crude extract
of this plant is used in inflammatory
and immune disorders
Triptolide andTripdiolide

29. Phyllanthostatin and
phyllanthoside
 A complex mixt. with marked antitumour
properties
 Obtained from the root of central
American tree, Phyllanthus cuminatus

30. Mechanism of action of antiMechanism of action of anti
cancerous drug…..cancerous drug…..
 Mechanism of action differ widely among various
chemotherapy agents
 Because they have different chemical structure
 majority of cancer chemotherapy drugs act by inhibiting
the nucleic acid synthesis
 there is no common feature to explain their biological
activity
 They can act as Mitotic poison, DNA inhibitors or
Alkylating agents

31. Mitotic poisonsMitotic poisons
Colchicum speciosum Gloriosa superba
 Colchicine, Podophyllotoxine &Vincristine
 They act by binding to tubulin (protein in mitotic spindle)
 During mitosis, the chromosome separate with the assistance of
these microtubules

32. DNA Inhibitors
 Camptothecin
 Inhibit DNA synthesis and replication through
enzyme topoisomerase I.

33. Alkylating agent
 A large number of natural tumor inhibitor acts as alkylating agent
become they posses highly electrophilic centers and their action is
through alkylation of nucleophilic group in the enzyme that control
cell division.
 Eg; Cucurbitacin, Bruceantin, Triptolide, Elephantopin
 Most of these compounds are cytotoxic killing both normal and
cancer cell.

34.  Antioxidants
 Free radical scavengers
 Inhibitors of (lipoxygenase & urokinase )
enzymes involved in cell division
Action of Phytochemicals isolated fromAction of Phytochemicals isolated from
folk medicines…..folk medicines…..

35. Curcuma
 Curcumin, a natural component of the
rhizome of curcuma has emerged as one
of the most powerful chemopreventive
and anticancer agents.
 Its biological effects are antioxidant and
anti-inflammatory

36.  Artemisinin, is a natural
product from antimalarial
Chinese herb Artemisia
annua L.
 Artemisinin and its
derivatives are active
against cancer cells. (Li. et
al, 2008).
Artemisia

37.  Annona glabra (pond
apple), a tropical tree
growing wild in the
Americas and Asia.
 Used in traditional medicine
against several human
ailments, including cancer.
(Cochrane et al, 2008).
Pond Apple

38. The seed of Strychnos nux-vomica
(Loganiaceae) has been used in
traditional Oriental medicine as a
folk remedy for the treatment of
cancer.
water extract of Strychnin seeds
affect the growth of human gastric
carcinoma cells. (Lee et al, 2008).
Nux-vomica

39. Dandelions
 Taraxacum, commonly
known as dandelions, have
a history of use in Chinese,
Arabian and Native
American traditional
medicine, to treat cancer.
 Crude extract of dandelion
leaf (DLE) decreased the
growth of breast cancer
cells

40.  Brucea javanica fruit is
reported to have anticancer
properties in Chinese medicine
and its extract has been shown
to possess anti proliferative on
human carcinoma cells.
 These findings are significant
in the development of
traditional Chinese medicine as
an alternative treatment for
pancreatic cancer (Lau et al,
2008).
Brucea

41. Some food materials with anti
cancerous property …….

42. Green TeaGreen Tea
 Numerous in vivo and in vitro studies
indicate strong chemopreventive effects
for green tea and its constituents against
cancers of various organs.
 (-)-Epigallocatechin-3-gallate (EGCG),
the major catechin in green tea, appears
to be the most biologically active
constituent in tea with respect to
inhibiting cell proliferation

43.  Ginger is a common condiment for
various foods and beverages.
 Some pungent constituents
(gingerol, zingerone and paradol )
present in ginger exhibit cancer
preventive activity.
Ginger

45. Fenugreek
 A naturally occurring edible spice as an anticancer agent.
 The extract from the seeds of fenugreek, is cytotoxic in vitro to a
panel of cancer but not normal cells.

46. Flaxseed oil
 Flax lignans belonging to the phytoestrogens are metabolised
after ingestion into enterolignans that may offer a protection
against the onset and development of hormono-dependant
cancers.

47. Flaxseed oil
 Flax lignans belonging to the phytoestrogens are metabolised
after ingestion into enterolignans that may offer a protection
against the onset and development of hormono-dependant
cancers.

48. sesame seed
 The mammalian lignans, which are produced by the
microflora in the colon of humans and animals from
precursors in foods, have been suggested to have potential
anticancer effects
 Sesame seed, alone and in combination with flaxseed,
produces mammalian lignans equivalent to those obtained
from flaxseed alone.

49. Soybean
 The soy isoflavones have antiproliferative effects on a variety
of cancer types.
 Lunasin of soy is a novel seed peptide for cancer prevention.
 Recent studies have demonstrated a direct effect of soy
saponins on cancer cells

50. Tomato
high consumption of tomatoes effectively lowers the risk
of reactive oxygen species (ROS)-mediated diseases
such as cardiovascular disease and cancer by improving
the antioxidant capacity.

51. Strawberry
Compounds in
strawberries have
demonstrated
anticancer activity
in several different
experimental
systems, blocking
initiation of
carcinogenesis, and
suppressing
progression and
proliferation of
tumors.

52. Citrus fruits
 flavonoids (hesperidin)
have a protective effect
against cardiovascular
diseases and some types
of cancer.
 Limonoids are a
prominent group of
secondary metabolites in
citrus fruit with
anticancer effect

53. Cruciferous vegetables
 Indole-3-carbinol (I3C), a naturally occurring
compound found in vegetables of the Brassica genus, such as
broccoli and cabbage, is a promising anticancer agent
 Cruciferous vegetables decreased the risk of breast cancer by
40 percent.

54. Crude extract
Solvent extraction
(inactive materials removed)
Structure of active cpd. is elucidatied
MS, NMR, IR, UV and X-ray crystallography
Treatment with weak acids/bases
Column chromatography
TLC, HPLC
Pure active ingredient
Isolation and purification of active ingredient

55. Purified natural product
tested against a range of standard experimental
neoplasms
preclinical toxicological studies
(large amounts of material will be required)
clinical studies
high therapeutic index and low side effects

57. Number of screens
Preliminary screening test 25,000
(per year)
Preclinical testing 8-12
Clinical trials 6-8
Slightly less than half of these may be plant-derived.

58. Availability of natural source
 Availability of the plant source has to be ensured
 If common, collected from wild, but commercial cultivation is
better
 Search for alternate source – related species
 Synthesis of active chemical through tissue culture – best
option

59. Conclusion
 Though the antitumour screening programmes have resulted in the
identification of a number of antitumour agents, only small number of
drugs have been developed
 Majority of these drugs are effective against rapidly proliferating
tumours
 However, slow growing tumours still respond poorly to chemotherapy
 Rapidly dividing natural tissues suffer toxic effect from the
administered drug , leading to the major side effect in cancer
chemotherapy like bone marrow repression, nausea, vomiting etc

60. • All these facts points out to the need for the development of drugs
that will separately and specifically affect the human cancer tissues
without damaging any normal tissue
 Ayurvedic therapy was found to be able to cure chronic diseases
better, which were previously not amenable to treatment by western
medical practices.
 Its systematic study and understanding is also worth considering by
pharmaceutical industries in order to develop their active ingredients
as allopathic drugs for cancer treatment.