Herbal Medicine For Cancer therapy

1. Herbal Medicine for
Cancer Therapy
Ass.Prof./Marwa Fayed

2. Natural methods for treatment of
cancer
Natural medicine aims to restore body’s ability to protect,
regulate and heal itself. This looks at your physical,
mental and emotional well-being. It is also called as
Phytomedicine, Phytotherapy or botanical therapy.
Alternative therapy that is followed by the cancer
patients is Herbal Medicine.

3. • More than 200 Complementary Therapy methods are
classified into five categories by the National Center for
Complementary and Alternative Health (NCCAM):
1. Alternative and Medical system (traditional Chinese
medicine including acupuncture and qigong, homeopathy,
ayurveda).
2. Body-mind therapy (bio-feedback, hypnosis,
relaxation/meditation, music, imagery, prayer/spirituality).
3. Biologically based therapies (herbal therapy, high-dose
vitamins, special diets).
4. Energy therapies (therapeutic touch, reiki).
5. Manipulative and body-based therapies (massage, exercise,
chiropractic, hydrotherapy, reflexology, acupressure).

4. HERBS

5. Catharanthus roseus
Catharanthus roseus belongs to the family
Apocynaceae.
- The plant has been extensively used in traditional
medicine since a long time. Ayurvedic medicines have
been prepared from various parts of the plant like the
stem, leaves, flowers, and roots.
- Extracts of the plant have been reported to be used
for treatment of many ailments like ocular
inflammation, diabetes, hemorrhage, in treatment of
insect stings, and cancers.
- It contains more than 120 terpenoid indole alkaloids
(TIAs), several of which have exhibited strong
pharmacological properties.
- Some of these alkaloids are used widely in modern
medicine as immunosuppressive and antitumor
agents.

6. • The Catharanthus alkaloids have proved to be of utmost
importance in clinical medicine, and mainly, Vincristine
(VCR), Vinblastine (VLB), and Vinorelbine (VRL) form
essential components of many standard chemotherapy
regimens.
• Vincristine is used mainly for Hodgkin’s lymphoma,
• Vinblastine is effective in case of childhood leukaemia.
• These alkaloids arrest proliferation of cancer cells by:
- binding to tubulin filaments in the mitotic spindle.
- induce apoptosis (programmed cell death)
- and hence inhibit spread of many types of cancers like
breast, ovary, lung, colon, rectum, testis,
neuroblastoma, Hodgkin’s disease and leukaemia.

7. Podophyllum
Podophyllum hexandrum Royle belongs to the family Berberidaceae.
Nowadays, it has been termed as a critically endangered medicinal plant.
It is native to eastern Asia.
All plant parts, except the fruit, are poisonous. It is even capable of
causing unpleasant indigestion when ingested.
Rhizomes of P. hexandrum provide several lignans which possess
antitumor activity.
Podphyllotoxin is an active cytotoxic natural product used as starting
natural compound for the synthesis of anticancer drugs like etoposide and
teniposide.

8. • The mechanism of action of Podophyllotoxin is by:
- inhibition of microtubule assembly.
- However, the anticancer action of etoposide and
teniposide is due to their interaction with DNA and
inhibition of DNA topoisomerase II.
These drugs which are derived from the plant
constituents are used against lung cancer, testicular
cancer, neuroblastoma, hepatoma and many others.
However, the major setback in using these for
treatment is their cytotoxicity for normal cells and as a
result lack of selectivity against cancer cells.

9. Ocimum
Ocimum grows as a small herb throughout India and is commonly known
as Tulsi in Hindi.
Traditionally, different parts of the plant like leaves, stem, flower, root,
seeds, and sometimes even whole plant have been used for the
treatment of various ailments like bronchitis, bronchial asthma, malaria,
diarrhea, dysentery, skin diseases, arthritis, painful eye diseases, chronic
fever, insect bite.
Eugenol (1-hydroxy-2-methoxy-4-allylbenzene), which is an active
constituent present in it, has been observed to be capable of providing
therapeutic properties to the plant. It also possesses antifertility,
anticancer, antidiabetic, antifungal, antimicrobial, hepatoprotective,
cardio-protective, antiemetic, antispasmodic, analgesic, adaptogenic, and
diaphoretic activities.
Leaf extract prepared from O. sanctum has been reported to protect
against chemical carcinogenesis using some of the mechanisms of action
as antioxidant, modulating phase I and II enzymes, and antiproliferative
activity.

10. Allium sativum
Allium sativum has been used for treating ailments as a
home remedy since ancient times. It exerts many
beneficial effects such as antimicrobial, antithrombotic,
hypolipidemic, antiarthritic, hypoglycemic and antitumor
activity.
The plant shows potential against cancer due to the
presence of organosulfur compounds.
Alk(en)yl sulfide components provide the characteristic
flavor present in garlic. Diallyl trisulfide is a major
constituent of the garlic oil. It has been reported that the
growth of human colon cancer cells HCT-15 and DLD-1 is
significantly suppressed by diallyl trisulfide.

11. • The results showed that diallyl trisulfide shows
anticancer effect for garlic eaters.
- There are multiple mechanisms present for
organosulfur compounds (OSCs) to exert their anti-
carcinogenic properties by:
- modulation of carcinogen metabolism,
- inhibition of DNA adduct formation,
- upregulation of antioxidant defences and
- DNA repair systems, and
- suppression of cell proliferation by blocking cell cycle
progression and/or inducing apoptosis.

12. • Garlic with its rich array of bioactive OSCs offer
promise as potential chemo-preventive and
chemotherapeutic agents.
• S-allylcysteine, an organosulfur compound derived
from garlic has been reported to retard the progress
of both chemically induced as well as transplantable
tumors in several animal models.

13. Taxus baccata
Taxol (Paclitaxel) and Taxotere (docetaxel) are included among the
important anticancer drugs used in cancer chemotherapy.
The anticancer activity of these is due to: their ability to cause
mitotic arrest in cancer cells, leading to apoptosis caused by
inhibition of the depolymerization of microtubules.
Although both drugs possess potent antitumor activity, treatment
with these often results in few undesirable side effects, as well as
multidrug resistance (MDR).
Paclitaxel (Taxol) is a widely used anticancer isoprenoid
synthesized by the secondary metabolism of Yew (Taxus sp.) trees.

14. Docetaxel, is a new semi-synthetic anticancer agent derived from
bacatin III of the needles of Taxus baccata.
Its novel mechanism of action has been investigated and described; it
binds to tubulin and hence induces its polymerization and promotes
stable microtubule formation.
Preclinical and phase II studies have reported docetaxel to be active
against NSCLC (non small-cell lung cancer). A taxane, diterpenoid 2-
deacetoxytaxinine J (2-DAT-J) 1 has been derived from the bark of
Himalayan yew or Taxus baccata L. spp. wallichiana and its anticancer
potential has been investigated against breast cancer cell lines (MCF-7
and MDA-MB-231). It exhibited significant in vitro activity against breast
cancer cell line. Few novel taxoids have also been derived from the
naturally occurring 2-DAT-J (1) and these also have been investigated for
their anticancer effects.

15. Curcuma longa
Curcumin (diferuloylmethane), a polyphenol natural product
obtained from the rhizome of Curcuma longa, and the major
active constituent of the dietary spice turmeric, is currently being
checked for its potential as a novel anticancer agent.
Many researchers have reported its pharmacological properties
like: chemosensitizing, radiosensitizing, wound healing,
antimicrobial, anti-viral, anti-fungal, immuno-modulatory, anti-
oxidant and anti-inflammatory.

16. • Another active component derived from Curcuma longa is tetra-
hydro-curcumin (THC), a major colourless metabolite of curcumin.
• It also possesses antidiabetic, anti-inflammatory, and antioxidant
activity.
• Curcumin exerts its anticancer properties using various mechanisms
like:
- arresting cell cycle,
- inhibiting inflammatory response and
- the oxidative stress, and
- by inducing apoptosis in cancer cells,
- through mediated cell cycle arrest.

17. Also, it has been proved that it possesses marked antiangiogenic properties. It is also
capable of potentiating the growth inhibitory effect of cyclo-oxygenase (COX)-2
inhibitors and some other traditional chemotherapy agents.
Recently, it has been shown that curcumin inhibits phosphorylation of p70 S6 kinase 1
(S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1),
downstream effector molecules of the mammalian target of rapamycin complex 1
(mTORC1) in numerous cancer cell lines. It has also been observed that curcumin is
capable of dissociating raptor from mTOR, which eventually results in inhibition of
mTORC1 activity. Therefore, it has been hypothesized that curcumin can be a
representative of a new class of mTOR inhibitors. Curcumin is also reported to inhibit
breast cancer cell motility and invasion by directly interfering with the function of alpha
(6) beta (4) integrin, and it has been suggested that it has potential to serve as an
effective therapeutic agent in tumors that overexpress alpha (6) beta (4).
Curcumin has shown activities in accordance to some of the recently discovered tumor
necrosis factor blockers like HUMIRA, vascular endothelial cell growth factor blocker
(AVASTIN), human epidermal growth factor receptor blockers (GEFTINIB), and a HER2
blocker (HERCEPTIN). So taking into consideration the recent scientific ideology that
multitargeted therapy is more beneficial as compared to monotargeted therapy for
diseases, curcumin can be easily be regarded as an ideal “Spice for Life”.

18. Zingiber officinalis
Ginger, the rhizome of Zingiber officinalis, is a widely used
species of the ginger family. It is a common condiment
used in India in various foods and beverages. It has been
used medicinally since 2500 years.
It has been traditionally used for many different human
ailments like digestion, diarrhea, nausea, common colds,
fever, rheumatic disorders, gastrointestinal complications,
motion sickness, diabetes, and cancer.
Some pungent constituents present in it have potent
antioxidant and anti-inflammatory activities, and some
also exhibit cancer preventive activity.

19. The anticancer properties of ginger are explained by the
presence of certain non-volatile pungent Vallinoids, [6]-
gingerol and [6]-paradol, as well as some constituents
like shogaols, zingerone, paradols, and gingerols, and so
on.
The chemopreventive effects exerted by these are often
linked to their antioxidative and anti-inflammatory
activities.
Many anti-inflammatory and chemopreventive
chemicals like these, act against cyclo-oxygenase-2
(COX-2).

20. • It has been reported that these substances also inhibit
tumor-promoter-stimulated inflammation, TNF-alpha
production, and activation of epidermal ornithine
decarboxylase in mice. In another research, [6]-gingerol
and [6]-paradol suppressed superoxide production
stimulated by TPA (12-O-tetradecanoyl-phorbol-13-
acetate) in differentiated HL-60 cells .
• [6]-Gingerol and [6]-paradol have been reported to
exert inhibitory effects on the viability and DNA
synthesis of human promyelocytic leukemia (HL-60)
cells.
• The cytotoxic and antiproliferative effects of both were
linked to apoptotic cell death.

21. Piper nigrum
Black pepper (Piper nigrum) is widely used as a spice
throughout India. It has a characteristic biting quality due
to the presence of a pure and pungent alkaloid, Piperine.
- It acts as an antioxidant, antimutagenic and anticancer
agent.
- Apart from being used as dietary agent, black pepper is
used for a variety of purposes such as medicinal,
preservative, and in perfumery.
- It has been observed that piperine is capable of
suppressing benzo-pyrene-induced lung cancer in Swiss
albino mice.

22. • It has been reported that administering piperine to
tumor-induced mice significantly lowers the phase I
enzymes and rise in glutathione-metabolizing enzymes.
This indicated antitumor and anticancer effect of
piperine.
• It has been suggested that piperine can extend its
chemopreventive effect by controlling and altering the
protein bound carbohydrate levels, as these are
indicators of tumorigenesis.
• The most important phenomenon of piperine has been
exerting its inhibitory effect on enzymatic drug
biotransforming reactions in liver. It inhibits hepatic and
intestinal aryl hydrocarbon hydroxylase and UDP-
glucuronyl transferase. It has been observed to enhance
the bioavailability of a number of therapeutic drugs by
this property.

23. Black Tea
Tea is a widely consumed ancient beverage throughout the
world, and black tea exerts many biological effects on the
organisms.
It is a potent antioxidant due to its free radical-scavenging
and metal-chelating properties. There are a number of
polyphenols present in black tea which include theaflavin
(TF), theaflavin-3-gallate (TF-2a), theaflavin-3′-gallate (TF-
2b), thea flavin-3,3′-digallate (TF-3), theaflavin gallate
(TFG), and theaflavin digallate (TFdiG).
It has also been suggested that the gallate structure of
theaflavins is important for growth inhibition in tumor
cells. So by virtue of all these, it can prevent inflammation,
clastogenesis, and several types of cancer.

24. • It reduces DNA damage and mutagenesis caused as a
result of oxidative stress or due to the presence of pro-
mutagens, through various mechanisms like:
- antioxidation,
- blocking activation pathways of mutagens,
- suppression of transcription of enzymes involved.
- Nitric oxide production was reduced by theaflavins
present in black tea. It occurs mainly by suppressing
inducible nitric oxide synthase by blocking nuclear
translocation of the transcription factor NFκB as a
result of decreased IκB kinase activity.

25. Green tea
Green tea has been found to be rich in polyphenolic compounds
with catechins being the major constituent.
The protective and preventive actions of green tea are mainly due
to the presence of polyphenols like epigallocatechin-3-gallate
(EGCG), epicatechin, epicatechin-3-gallate, epigallo-catechin (EGC).
These polyphenols comprise about one-third of the weight of the
dried leaf of the plant.
These catechins have been reported to possess diverse
pharmacological properties including antioxidative, anti-
inflammatory, anticarcinogenic, antimutagenic, anti-arteriosclerotic
and antibacterial effects.

26. • In the GI tract, green tea was observed to:
- activate intracellular antioxidants,
- inhibit procarcinogen formation, and
- suppress angiogenesis, metastasis, and cancer cell
proliferation.
• Tea consumption has been reported to be inversely
proportional to the occurrence of various cancers like that
of the stomach, oral, and colon.

27. The major contributor in providing chemo-preventive abilities to
green tea is epigallocatechin-3-gallate (EGCG).
- Its mechanism of action includes:
- inducing apoptosis and
- enhancing cell growth arrest by altering the expression of cell
cycle regulatory proteins,
- activating killer caspases,
- altering β-cell lymphoma (βcl-2) family member expression and
- inhibiting nuclear factor kappa-B (NF-κB)
- Metastasis in tumor cells was inhibited by exerting effects on
urokinase and matrix metalloproteinases.

28. Capsicum
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), is an
alkaloid produced mainly from the genus Capsicum.
It causes the pungency factor and is a bioactive molecule of food
and also of medicinal importance. It induces excitation of
nociceptive terminals which are mainly involved in pain
perception.
It is also useful as a counterirritant, antiarthritic, analgesic, and
antioxidant.
It has also been proven that capsaicin has chemo-preventive as
well as anticancer properties.

29. • Another component of capsicum is Capsiate, a non-
pungent capsaicin analogue, and its dihydro-derivative
dihydro-capsiate.
• A cancer-specific cell surface protein, tNOX, has been
reported as a suitable target for low-dose cell killing
using capsicum vanilloid. This protein is known to be
associated specifically with cancer cells and is absent
from normal cells. Its activity is linked to cancer growth.
When the protein is blocked, cancer cells die as a result.
Vanilloid capsaicin is a potent inhibitor of this protein.

30. The effectiveness of inhibiting the protein increases 10-fold to
100-fold when catechin-vanilloid combinations are used as
compared with using either of themalone.
It has been reported that capsaicin possesses ability to act as a
novel inhibitor of angiogenesis. It has been shown that in vitro,
capsaicin, capsiate, and dihydro-capsiate:
- inhibit vascular endothelial growth factor (VEGF)-induced
proliferation,
- DNA synthesis, chemotactic motility, and capillary-like tube
formation of primary cultured human endothelial cells.

31. Cannabis sativa
Cannabinoids, synthesized from Cannabis sativa, exert an
effect on human body by mimicking endogenous
substances—the endocannabinoids which activate
specific cell surface receptors.
The cannabinoids prove their potential as antitumor drugs
mainly due to their mechanism which involves:
-limiting cell proliferation and inducing tumor-selective
cell death.
Synthetic cannabinoids, like nabilone and dronabinol, are
thought to have pro-tumor effects in vivo because of their
immunosuppressive properties, which include inhibiting
tumor growth and migration, angiogenesis, metastasis,
and inflammation.

32. • Delta(9)-tetrahydrocannabinol (THC) has potential to
treat the symptoms and side effects of cancer.
• Some others which are known include Cannabidiol
(CBD) and Cannabigerol (CBG).
• Cannabinoids are known to induce palliative effects
mainly by preventing nausea, vomiting, and pain and
improving appetite.

33. Cannabinoids inhibit tumor cells growth in vitro and in
vivo experimental models mainly by modulating key cell-
signalling pathways.
Cannabinoids generally do not produce toxic side effects
of conventional chemotherapies.

35. • https://dergipark.org.tr/en/download/article-
file/329464
• https://www.researchgate.net/publication/2845832
08_Indian_Herbal_Medicine_for_Cancer_Therapy_a
nd_Prevention
• https://www.sciencedirect.com/science/article/pii/S
2221169117308730