REVIEW ARTICLE Overview of Cancer and Medicinal Herbs

used for Cancer Therapy

Anupama Thapliyal, Roop Krishen Khar, Amrish Chandra
Department of Pharmacy, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, India

Abstract

Cancer is a disease in which abnormal cells proliferate in the body. It is a group of various diseases involving
uncontrolled multiplication and division of abnormal cells in the body. These abnormal cells form malignant
growths which called neoplasm. Nowadays, cancer considered as one of the most prevalent diseases in the world,
and its mortality is increasing. It is necessary to investigate new strategies to prevent and treat disease. Herbal
medicines block critical biochemical pathways converting normal cells to cancer cells for treatment. Herbal
medicines block signal transduction in cancer which is a primary channel, by such as controlling nuclear factor-kB
signaling pathway, protein tyrosine kinase pathway, and mitogen-activated protein kinases signal pathways.
The various study reported that people with cancer commonly use herbal products because of no side effects
on healthy cells. Herbal medicine is one of the most widely used alternative therapies by people with cancer.
Clinically proven herbal remedies help to prevent or relieve the symptoms of cancer or treatment side effects by
a conventional method. We have discussed various medicinal herbs found in India which have the potential to
be used in cancer therapy. This present review will focus on the different medicinal plants containing chemical
constituents used in the treatment of cancer with their possible mechanism of action.

Key words: Anticancer compounds, cancer, herbal-drug interactions, medicinal herbs

INTRODUCTION years. Surgery and radiotherapy are a successful treatment

in many cases, and chemotherapy is moderately efficacious
The disease was first named cancer by for some advanced cancers. In general, a modification
the Greek physician Hippocrates, Father made in cure and survival rates for these. Modern cancer
of Medicine, who applied Greek words therapy identifies that not presently available treatments
“carcinoma” and “Karakinos” to describe a can cure every malignant tumor. Hence, treatment needs
tumor.[1] Cancers are a family of diseases that to be carefully chosen to maximize the chance for a cure
involve abnormal growth of the cells which while retaining a maximum of life quality. Significant
spreads to other parts of the body.[2] Cancer was steps toward successful treatment were made with specific
named about the type of tissue from which they cancers. Those modifications had a small effect on the
arise.[3] Tumors resulting from epithelia are impact of cancer on the overall population but have helped
called “carcinomas.” In both genders, cancers many individuals, often young people and children. Hence,
of the lung, colon, and rectum are the most better knowledge of the molecular and cellular basis
significant problem. Breast cancer is common will eventually open the door to successful treatment of
in women and prostate cancer in men. Breast the primary carcinomas, as will the development of new
cancers are not quite as prevalent as these drugs and new therapies based on the results of molecular
biological cancer research.[4]
“major four” diseases. They include carcinomas
of the bladder, stomach, liver, kidney, pancreas,
esophagus, and cervix and ovary in women.
Epidemiology of cancers is most natural Address for correspondence:
skin cancer. They are rarely deadly, with the Amrish Chandra, Department of Pharmacy, Amity
important exception of melanoma. Testicular Institute of Pharmacy, Amity University, Noida,
Uttar Pradesh, India. Phone: +91-9971117009.
cancer is the most frequent cancer affecting
E-mail: [email protected]
young adult males.[4]
Received: 22-06-2017
Unfortunately, neither incidence nor mortality
Revised: 08-02-2018
of human cancer has been much depreciating
Accepted: 18-02-2018
by conscious human intervention over the past

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 Thapliyal, et al.: Medicinal herbs for cancer therapy

CAUSES OF CANCER • Immortalization (growth beyond replicative senectitude)

• Conquering into different tissue layers and other tissues
The majority of cancers are due to environmental factors. • Metastasis to local lymph nodes and distant tissues.[6]
The main reason of cancer are related to the environmental,
lifestyle or behavioural exposures. The ecological factors
that contribute to cancer death include chemicals in tobacco CLASSIFICATION OF CANCER
smoke, radiation, such as ultraviolet rays from the sun,
obesity, stress, lack of exercise and environmental pollutants. Cancer is classified regarding the site of origin of the
Exposure to substances linked to specific types of cancer such malignant cells; the histology or cell lysis (called grading);
as exogenous chemical, physical, or natural carcinogens.[5] and the extent of disease (called staging).[7]

Site of cancer origin

CLASSIFICATION OF HUMAN
CARCINOGEN This classification describes the tissues in which the cancer
cells begin to develop. Following are the examples of the
a. Chemical carcinogens: Nickel, cadmium, arsenic, location of tumorgenesis categorization.
nitrosamines, trichloroethylene, arylamines, • Adenocarcinoma (prostate cancer) - originates in gland
benzopyrene, aflatoxins, and reactive oxygen species. cells.
b. Physical carcinogens: Ultraviolet irradiation (specifically • Blastoma (embryonal carcinosarcoma) - arises in fetal
UVB), ionizing radiation. tissues.
c. Biological carcinogens: Human papillomavirus, Epstein– • Carcinoma (cancer) - originates in epithelial tissue.
Barr Virus, hepatitis virus B, Helicobacter pylori, etc. • Myeloblastic Leukemia - occurs in tissues which
d. Endogenous processes: DNA replication, metabolic generate cells of blood.
reactions, and chronic inflammation. • Lymphoma (malignant neoplastic disease) - occurs in
tissue.
• Myeloma - a tumor of the bone marrow composed of
CANCER BY GENETIC CHANGES cells normally found in bone marrow.
• Sarcoma - originates in connective tissue such as bone,
Changes in genes cause disease. The mutation in the different cartilage, and muscle.[7]
types of a gene often are associated with different forms
of cancer. These altered or mutated genes can be broadly
Grading
classified into three groups, such as proto-oncogenes, tumor
suppressor genes, and DNA repair genes. The degree of malignancy of a tumor is estimated by grading
Proto-oncogenes: systems. The abnormal behavior of the cells determines the
grade of cancer. Increasing abnormality of cells increases the
1. These genes involved in healthy cell growth and division. degree, from 1 to 4. The most general scheme is G grading,
Alteration in these genes may become cancer-causing which ranks from G0 to G4.
genes. • G0 denotes normal differentiation and no cellular atypia.
2. Tumor suppressor genes involved in controlling cell • G4 denotes cellular morphology entirely different from
growth and division. the normal tissue.
3. DNA repair genes participate in repairing damaged • G1, G2, and G3 grades are defined well-differentiated,
DNA. Mutation in these genes develops additional moderately and poorly differentiated.[7]
variation in other genes. These mutations may cause the
cells become cancerous.[5,6]
Histological classification

CHARACTERISTICS OF CANCER AND Cancer is classified histologically by the location of the tumor.
Histological typing of tumors performed by evaluating their
CANCER CELLS
morphology. A tumor is histologically classified from surgical
specimens. Biological markers improved tumor classification
Human diseases share several essential features:
by histopathological classification. For hematological
classification, genetic science techniques are used.[8]
• Increased cell proliferation (often autonomous)
• Insufficient apoptosis
• Altered cell and tissue differentiation Staging classification
• Altered metabolism
• Genomic instability The extension of a tumor is defined by “staging.”

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 Thapliyal, et al.: Medicinal herbs for cancer therapy

Two types of stages were described as follows: Medicinal plants with anticancer activity
Clinical stage:
1. Before surgery, a clinical stage is defined by visual Cassia fistula
examination, pulsation, and various imaging techniques.
It is a plant also known as the golden shower in the family
These methods use ultrasound, X-rays, computed
Fabaceae. C. fistula had many medicinal properties such as
tomography, and magnetic resonance. “c” prefix denotes
purgative and laxative and was used for various disorders
it.
such as hematemesis, pruritus, leukoderma, and diabetes.[15,16]
C. fistula is a primary source of naturally occurring bioactive
Pathological stage:
compounds. Bioactive compound polyphenolics present in
2. After surgery performed, a more precise examination of
this plant proved to be important, non-toxic chemopreventive
the tumor can be made by inspection of the tumor site
agents against various oxidative stresses in both in vitro and
and by histopathological investigation of the specimen.
in vivo.[17,18]
The stage defined pathological stages, and “p” prefix
denotes it.
Terminalia arjuna
Mostly used and systematic staging system is the tumor, It is a tree of genus Terminalia representing a substantial
node, and metastasis system. tropical component of the family Combretaceae also known
as arjuna. Various Terminalia species had used in traditional
Cancer is classified by tumor size (T), the degree of node treatments of cancer. Photochemical luteolin, gallic acid, and
development (N), and distant metastasis (M), while others ethyl ester in T. arjuna provide scientific evidence supporting
remain in use for specific cancers.[8] the traditional medical application of extracts of this tree in
cancer treatments.[19]

CANCER TREATMENT Cissus quadrangularis

It is a medicinal plant belonged to family Vitaceae[20]
Methods of cancer treatment and known as asthisamhara in Sanskrit, meaning “which
will strengthen the bones.” The plant contains significant
Surgery and chemotherapy are considered as the most amounts of Vitamin C, carotene, anabolic steroid
common methods of cancer treatment; these methods substances, and column.[20] It is used as an antioxidant in
have severe side effects in use.[3] One of the biggest many applications.
problems in cancer treatment is gradually increasing the
resistance of cancer cells against treatment.[9] Therefore, Psoralea corylifolia
developing a new approach is one of the primary objectives
The seeds of P. corylifolia had used as an ancient Hindu
of immunopharmacological studies to improve cancer
remedy for leukoderma which belongs to family Fabaceae.[21]
treatment results.[10] Nowadays, herbal medicines have
The furanocoumarin psoralen from P. corylifolia seeds has
played a significant role in controlling cancer symptoms
been shown to be active against cutaneous T-cell lymphoma
and treatments with minimizing side effects.[11] Some
and cytotoxic in vitro to cultured mucoepidermoid
medicinal herbs induce apoptotic pathways through various
carcinoma cells of MEC-1 cell line.[22,23] P. corylifolia seed
mechanisms in cancer cells. Medicinal plant constituents
extract PCSE possesses an immunomodulatory activity
include vinca alkaloids (vinblastine and vincristine),
and increases in the cell-mediated and humoral immune
taxanes (paclitaxel and docetaxel), podophyllotoxin, and
responses.
its derivatives (topotecan and irinotecan). Camptothecins
have clinically used as plant-derived anticancer agents.[12,13]
Eclipta Alba
A list of marketed anticancer herbal medicines are given in
Table 1. E. alba is called Bhringaraja, considered a primary liver herb
in Ayurveda.[24] Hydroalcoholic extract of E. alba was shown
to possess antiproliferative, apoptotic, and anti-invasive
Herbal medicines in cancer treatment
activities.[24,25]
In India, herbal medicines have been used for centuries
Gymnema Sylvestre
to treat many different health problems. It includes plants
or mixture of plant extracts to treat illness and promote G. sylvestre is a plant that found in the forests of India.[26]
health. Herbal medicines are one of the most generally used Five water-soluble polysaccharides (GSP11, GSP22, GSP33,
complementary and alternative methods by people with GSP44, and GSP55) were obtained from G. sylvestre[26]
cancer.[14] having the potential of natural antitumor agents.

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Table 1: List of marketed anticancer herbal medicines

Class Drugs Plant source
Vinca alkaloids Vincristine Catharanthus roseus
Vinblastine (Apocynaceae)
Taxanes Paclitaxel Taxus brevifolia
Docetaxel (Taxaceae)
Epipodophyllotoxin Etoposide Podophyllum hexandrum
(Berberidaceae)
Camptothecin analogs Topotecan Camptotheca acuminata
Irinotecan (Nyssaceae)
Colchicine Demecoline Cocus Colchicum autumnale
(Liliaceae)
Maytansinoid Mcytanacine Maytenus buchananii,
Maytansine Morus serrata (Celastraceae)
Macrocyclic lactones Bryostatins Bryozoa Bugula neritina
Quassinoids Bruceantin brusato Brucea javanica (Simaroubaceae)
Curcuma Curcumin Curcuma longa (Zingiberaceae)
Flavonoids Vicenin Ocimum sanctum (Labiatae)
Orentin
Sesquiterpene Gossypol Gossypium barbadense (Gossypiaceae)
Ellipticine Ellipticine Ochrosia elliptica (Apocynaceae)
Phthalide isoquinoline alkaloid Noscapine Papaver somniferum (Papaveraceae)
Acetogenins Acetogenin Annona species (Annonaceae)

Tinospora cordifolia Capsicum annuum

This plant used in many drug preparation for general health C. annuum is widely used as vegetables and food colorants
and disease condition belongs to family Menispermaceae. Its which are a good source of carotenoid pigments.[32,33] The red
stem extracts showed phagocytic and reduced solid tumor carotenoids in paprika (C. annuum L.) are mainly capsanthin,
volume and successfully employed in many preparations capsorubin, and capsanthin 3,6-epoxide in which capsanthin
with immune stimulating activity.[27] and capsorubin have been reported to show antioxidative
activities.[34,35]
Curcuma aromatica
Mesua ferrea
C. aromatica having Curcuma genus belongs to family
Zingiberaceae has identified as having anti-inflammatory, M. ferrea known as “Nagakesara”[36] reported for
anti-oxidative stress, and anticancer properties.[28,29] The main antioxidant,[37,38] hepatoprotective,[39] analgesic,[40]
biological active components of C. aromatic which mainly antimicrobial, [41]
antivenom, [42]
anticancer,[43]
antiulcer,[44]
contains curcuminoids: Curcumin, bisdemethoxycurcumin, anti-inflammatory, [45]
antiasthmatic, [46]
and other several
and desmethoxycurcumin and sesquiterpenoids including activities. The study reported that the mixture of isolated
turmerone, germacrene, and β-elemene which were used for compounds, α-amyrin or β-amyrin and lupeol were isolated
cancer treatment.[28] from the dichloromethane extract of M. ferrea stems exhibited
anticancer activity against MCF-7, KB and NCI-H187 cancer
Symplocos racemosa cell lines.[47,48]
S. racemosa belonging to a family (Symplocaceae) is a
Boerhavia diffusa
traditional Ayurvedic medicine. The general names of
S. racemosa are astringent bark, Lodha, Godhra, rodhra, and B. diffusa Linn (Punarnava; family Nyctaginaceae) is an
lodhraka.[29] The study reported the vital ingredients such as abundant creeper found all over India. Extract of B. diffusa
phenol, flavonoids, triterpenoids, steroids, tannins, lignans, inhibited the proliferation of various cell lines of human and
and coumarins which are responsible for the anticancer mouse origin and had significant antiproliferative action in T-cell
activity of the plant extract.[30,31] mitogen (PHA as well as Con A) and antigen (purified protein

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 Thapliyal, et al.: Medicinal herbs for cancer therapy

derivative)-stimulated human peripheral blood mononuclear in the control points in G1 and G2 phases. Neoplastic cells
cell and immunosuppressive/antiproliferative activity.[49,50] are not capable of preventing cell division at the control
points (G1/S and G2/M), and proliferation of cells becomes
Terminalia bellerica deregulated.[61]
T. bellerica known as belleric myrobalan belongs to family
Combretaceae, found in grasslands and hills of Southeast Mitogen-activated protein kinases (MAPK) signal
Asia. This plant extract having several pharmacological pathways
effects including antibacterial, antimalarial, antifungal, anti-
HIV, antioxidant, and antimutagenic effects[50-53] reported MAPK signaling pathway induces signals for the division
anti-proliferative effects in cancer cell lines including breast of cells. Hence, carcinogenesis caused by deregulation of
cancer MCF-7, prostate cancer PC-3, and DU-145 cells.[54] MAPK signal pathways.[60] Such technique is applied to
T. bellerica contains chemical components, including gallic induce apoptosis.[62]
acid.[55,56] which has been shown to induce apoptotic cell
death in cancer cells.[57-59] Cyclooxygenase (Cox-2) pathways

Cyclooxygenase is known as a Cox-2 inhibitor which

MECHANISM OF HERBAL MEDICINE FOR catalyzed the prostaglandin synthesis. Inhibition of COx-2
TREATMENT OF CANCER affects the growth of tumor cells through inhibiting cell
proliferation.[63]
Medicinal herbs act through various mechanisms.
Intervention with microscopically small tubules
Disruption in cell signal transduction pathways
Microscopically small tubules are known as microtubules
Cancer is strongly associated with defects in signal- present in the cytoplasm of cells. Microtubules play a vital
transduction proteins which results in uncontrolled or role in preventing alignment of the daughter chromosomes
inappropriate cell growth. Herbal drugs block signal and consequently stop of mitosis at anaphase, which finally
transduction in cancer by various routes as following. followed by apoptosis.[1] It was reported that herbaceous
plant phytochemicals such as vinca alkaloids (vincristine and
vinblastine) and taxanes are important microtubulin-binding
Nuclear factor (NF-kB) pathways with activator factors.
protein (Ap-1)

Nuclear factor (NF-kB) with activator protein-1 (AP-1) are Topoisomerase inhibitor
transcription factors regulates many gene expression involved
in oncogenesis, apoptosis, etc. by extracellular signals. It Herbal drugs are having a crucial role in cancer treatment
is mainly a protein complex that regulates transcription with balancing capacity of topoisomerases. Camptothecins
of DNA, cytokine production and cell survival. Incorrect inhibit topoisomerase-I, and epipodophyllotoxins inhibit
regulation of NF-kB associated with cancer, inflammatory topoisomerase II.[1]
and autoimmune diseases.[60] Medicinal herbs inhibit the
growth of cancer cells by this mechanism, like botanical
extract of mountain ginseng inhibits the growth of lung SAFETY AND PHARMACEUTICAL
cancer cells through regulating NF-kB signaling pathway.[60] INTERACTIONS OF HERBAL MEDICINES

Protein tyrosine kinase (PTK) pathways Security is defined as a condition in which a substance or a
drug is targeted to be safe or dangerous and showing potent
effects against long-term and short-term side effects. Since
It is a type of enzyme that can transfer a phosphate group to
herbal products used plants, extracts, and mixtures which
a protein in the cell. Hence, it is called PTK. It functions as
are natural, so they were often safe for treatment. However,
an active and not active in many cellular reactions. It causes
in some cases, different adverse effects were reported by
growth in signal transduction to cells.[61]
administration of some herbal medicines through various
mechanisms such as direct toxicity of plant, allergy, plant
Modification in cycle of cell pollutants like lead, mercury, arsenic, and pharmaceutical
interactions with other medications.[64]
The natural and constant balance of cycle of cell ensures
standard cell escalation. The change in cell cycle concludes Herbal-drug interactions were particularly pertinent in
the tumor. Elongation of the cell cycle caused by the existence such cases like when cardiovascular medications such as

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 Thapliyal, et al.: Medicinal herbs for cancer therapy

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