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Tumor Inhibitors from

Dr. Najam-us-Sahar
• A mass of excess tissue that results from abnormal cell
• Tumors perform no useful body function.
• They may be benign (not cancerous) or malignant

• A term for diseases in which abnormal cells divide
without control.
• Cancer cells can invade nearby tissues and can spread
through the bloodstream and lymphatic system to other
parts of the body.

Cancer is a dreadful disease and is the second major cause of

deaths after cardiovascular diseases
The incidence of various forms of cancer is now rapidly
rising world wide
so combating this disease is of paramount importance to
public health
Cancer Causes
• Benzene and other chemicals
• Drinking excess alcohol
• Smoking
• Environmental toxins, such as certain poisonous mushrooms &
• Excessive sunlight exposure
• Genetic problems
• Obesity
• Radiation
• Viruses
Cancer treatments
Impact of chemotherapeutical agents

• They are highly reactive and non-selective

• They cause serious unpleasant side effects like
Nausea, vomiting, taste and smell changes, infection,
anemia, etc
• 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
Natural Products for treatment of Cancer

• WHO estimates that 80% of world population relies

on plant-based medicines for primary healthcare
• Safer
• More natural
• Holistic
• Symptom relief (pain, nausea)
Plant derived anticancer agents in
clinical use
Common names:
Madagascan periwinkle, Vinca, Sadabahar etc.

Botanical Source:
The Madagascan periwinkle, is the dried entire plant of
Catharunthus roseus has been variously designated Vinca
rosea and Lochnera rosea.

Vincristine & Vinblastine
• Leurocristine (Vincristine)
• Vinca leukoblastine (Vinblastine)
• First clinically used theraputic drug
• Used for treating a variety of cancers including leukaemia,
lymphomas, advanced testicular cancer, breast and lung
• Vincristine effective for treating acute childhood leukemia
• Vinblastine has been especially effective for treating
Hodgkin's disease

• Vinblastine is used mainly for the treatment of

generalized Hodgkin's disease and non-Hodgkin's

• Vincristine is used principally in the treatment of acute

lymphocytic leukaemia in children.

• It has other applications for lymphomas, small cell lung

cancer, cervical and breast cancers.

• The semi-synthetic vindesine is also used in the

treatment of acute lymphoid leukaemia in children.

• Vincristine has a superior antitumour activity compared

to vinblastine, but is more neurotoxic.

• Vinorelbine is a newer, orally active, semi-synthetic

anhydro derivative of 8'-norvinblastine with a broader
anticancer activity and lower neurotoxic side-effects than
the other Catharanthus alkaloids.
Paclitaxel (Taxol)

• Obtained from : Taxus brevifolia

• Bark
• Active against advanced breast
cancer, ovarian cancer and lung
• 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 lung cancer
Podophyllum peltatum

• Mayapple
• Podophyllum peltatum
• Perennial plant in the barberry family (Berberidaceae)
• Well known poisonous plant
• Traditional uses of mayapple:
• Rhizomes dried and ground to a powder
• Powerful purgative
• Also used to treat warts and tumorous growths on the skin
• Isolated from rhizome of
Podophyllum peltatum
Podophyllum emodi
Its semi synthetic derivatives are used
in the cancer treatment .
• Etoposide :cancer, lymphomas and
• Teniposide: paediatric cancer,
neuroblastoma, brain tumours
• Use in cancer chemotherapy:
• Resin from mayapple rhizomes used in cream to treat cancerous tumors,
polyps and granulations in traditional medicine
• Active Compounds in Rhizome
• Podophyllum peltatum rhizome contains
high concentrations of anticancer lignans and other cmpds
• podophyllotoxin
• a and b peltatin
• Another species - Podophyllum emodii
• podophyllotoxin
• a and b peltatin
• berberine an alkaloid which can be used to treat fevers
(including malaria) and as an antibiotic
• Mode of action of podophyllotoxin:
• Podophyllotoxin acts as a cell poison for cells undergoing mitosis
• Too toxic for chemotherapy use
• Used in creams as treatment for genital warts
• Genital warts caused by HPV (human papillomavirus) associated with
cancers of the genitals (squamous cell carcinomas)
• Side effects of podophyllotoxin:
• Adverse reactions to topical applications include burning,
• When the drug was being investigated as a chemotherapy agent, it
caused nausea, vomiting, fever, mouth ulcers, diarrhea, nervous
system problems, seizures, kidney damage, etc.
• Semi-synthetic derivatives:
• Etoposide and teniposide are derivatives of phyllotoxin that are much less toxic and
are safely used in chemotherapy
• Etoposide is much more widely used
• Both compounds block the cell cycle in at least two specific places
• Etoposide Marketed as VePesid or VP-16
• Administered intravenously or orally as liquid capsules
• Widely used to treat various types of cancer
• Testicular cancer which hasn't responded to other treatment
• First-line treatment for small-cell lung cancers
• Used for lymphomas and malignant melanomas
• Side effects of etoposide:
• Major side effects include hair loss, nausea, anorexia, diarrhea, and low leukocyte and
platelet counts
• Some people have severe allergic reactions to the drug
• Can cause genetic damage and may increase a patient's risk of developing leukemia
• Causes fetal damage and birth defects
Harringtonine and Homoharringtonine

• Alkaloid obtained from: Cephalotaxus harringtonia

• Used in China : acute leukaemia
• part: seeds
• Obtained from : Ochrosia elliptica
• Treatment of breast cancer
• Marketed in France
Colchicum autumnale

•Botanical name: Colchicum autumnale Linn

•Family: Liliaceae
•English name: Autumn Crocus, Meadow
•Urdu name: Suranjan Shireen
•Part used : Dried seed, Corm, Flower.
•Chemical class : ALkaloids
Chemical Constituents

•Fixed oils
•In treatment of gout
•In Treatnent of Leukaemia
•Osteoarthritis of knee
• Although colchicine is not clinically used to treat cancer
because of toxicity, it exerts antiproliferative effects
through the inhibition of microtubule formation by
blocking the cell cycle and triggering apoptosis.
• Colchicine can still be used as a lead compound for the
generation of potential anticancer drugs.
• Thus, numerous analogues of colchicine have been
synthesized in the hope of developing novel, useful drugs
with more favourable pharmacological profiles.
• Several colchicine semisynthetics are less toxic than
colchicine and research is being carried out on effective,
less toxic colchicine semisynthetic formulations with
potential drug-delivery strategies directly targeting
multiple solid cancers.
• Colchicine is a plant secondary metabolite extracted
from Colchicum autumnale.
• Several analogs of colchicine were designed and
synthesized namely, 3-demethyl colchicine,
colchicoside, thiocolchicocide that displayed improved
anticancer activity in comparison to native drug against
certain leukemic cells and solid tumors.
• Mechanistically, colchicine inhibits microtubule
polymerization by binding to tubulin, one of the main
constituents of microtubules.
• In another sense, availability of tubulin is necessary to
mitosis; hence colchicine effectively works as a “mitotic
poison” or spindle poison.
Rifamycin antibiotics
• Rifamycins are microbial-derived macrolides that were
isolated in 1957 from the actinomycete Streptomyces
mediterranei, obtained from the soil of the pine forests of
southern France
• Many natural and semisynthetic rifamycins inhibit the
virion RNA-dependent DNA polymerase (RT).
• Rifamycin B was reported active against murine sarcoma
virus (MSV) due to its RT, focus formation and cell
transformation inhibitory activities.
• Rifamycin antibiotics also inhibit the RT of Rauuscher
leukemia virus, preventing its leukomogenic activity
Macrolide antibiotics

• Clarithromycin (CAM) is a well-known macrolide

antibiotic available as a generic drug.
• CAM is traditionally used for many types of bacterial
infections and eradication of gastric infection
with Helicobacter pylori.
• Extensive preclinical and clinical data demonstrate a
potential role for CAM to treat various tumours in
combination with conventional treatment.
• The mechanisms of action underlying the anti-tumour
activity of CAM are multiple and include prolonged
reduction of pro-inflammatory cytokines, and anti-
• Immunostimulants plays an important role in virtually all aspects of cancer
immunotherapy, especially cancer vaccine development.
Anti-AIDS agents:

• Anti-HIV drugs are also used as cancer treatments.

• Azidothymidine was studied as an antineoplastic in the
1990s, but despite promising in vitro data, clinical trials
showed little antitumour activity
• Highly active antiretroviral therapy (HAART) has potential
antitumour properties against Kaposi's sarcoma
• HIV protease inhibitors are also a new class of anticancer
drugs with multiple effects
Antineoplastic Antibiotics

• Antineoplastic antibiotic is also known as anticancer or

antitumor antibiotic and it acts quite similar as
• The main difference between antibiotics
and antineoplastic antibiotics is the former one act on
bacterial cells, while the latter act on tumorous or
cancerous cells in human body.
• Antineoplastic antibiotic affects DNA synthesis and
replication by inserting into DNA strands or by
producing superoxide that cause breakage in DNA
strands and prevent the tumorous or cancerous cells to
divide further.
• Cytotoxic Antibiotics
• Cytotoxic antibiotics are made from natural
• These drugs act during multiple phases of the cell
cycle and are considered cell-cycle specific.
• There are several types of antitumor antibiotics:
anthracyclines, chromomycins, and an antibiotics
series called miscellaneous, which includes
mitomycin and bleomycin
Folk medicines as potential anticancer
• 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.
Butea monosperma

• Famous tree known as - the flame of forest

• Flavone glycoside from leaves
• Inhibited tumour cells in experimental models
Withania somnifera

• Withanolides
• Present in the whole plant.
• They are believed to be immuno modulators having
anticancer activity
DNA Inhibitors
• Camptothecin
• Inhibit DNA synthesis and replication through enzyme
topoisomerase I
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
• Eg; Cucurbitacin, Bruceantin, Triptolide, Elephantopin
• Most of these compounds are cytotoxic killing both
normal and cancer cell.
Some food materials with anti
cancerous property
Green Tea

• A recent study from Japan demonstrates that green tea

goes way beyond it's role as a well-known antioxidant.
• One of the factors that sets cancer cells apart from
normal cells is that they have telomerase, an enzyme that
maintains telomeres on the ends of DNA.
• Most normal cells do not have telomerase to maintain
their telomeres.
• Everytime a normal cell divides, telomeres are lost.
• ECGC – telomerase inhibitor
• Destroy cancer cells
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

• The soy isoflavones have antiproliferative effects on a variety of cancer

• Soy seed is used for cancer prevention.
• Recent studies have demonstrated a direct effect of soy saponins on
cancer cells
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.


Compounds in strawberries have demonstrated anticancer activity in several

different Experimental systems, blocking initiation of carcinogenesis, and
suppressing progression and proliferation of tumors.
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
Isolation and purification of active ingredient