Anti cancer thesis

Anti Cancer Activity of

Medicinal Plant On breast cancer or blood cancer

MBT Project Thesis-Part 1

Guided by Prepared by

Dr. Nilesh Ranjan Maity,Ph.D Sk Abu Raihan Abdullah

Professor MBT , 3rd

Semester

Department of Biotechnology NITMAS

NITMAS

INTRODUCTION

I. Overview Cancer is one of the most serious health problems worldwide, affecting

individuals from different sexes, ages, and races. It is a group of diseases,

characterized by uncontrolled cellular growth with frequent cancer cells

invasion to different body parts and spreading to other organs,

a process referred to as Metastasis. Metastasis is the major cause

of cancer related mortality.

In 2005, cancer was the second leading cause of death among both men and

women and accounted for 13% of the total 58 million deaths worldwide . In

2006, about 10.9 million new cancer cases are expected to be diagnosed

worldwide and more than 7.8 million cancer patients may die .

Cancer is also a problem of economical dimensions with a very high level of

expenses associated to it. For example the National Institute of Health, USA

estimates that an overall of $209.9 billion were invested worldwide in 2005,

for the sake of cancer research and management .

Cancer is a heterogeneous illness which can originate from many different

organs of the human body. However, the most frequent cancer types in the

world are lung, prostate, stomach, colorectal, and esophagus in men; and

breast, lung, stomach, colorectal and cervical in women .

Prostate cancer is the most frequently diagnosed and the second leading cause

of cancer death among men, with 234460 new cases estimated to occur in USA

during 2006, and 27350 American men will die as a result of this disease(3). In

Palestine, the mortality rate of prostate cancer was 1.4 per 100000 during the

period from January, 1995 to December, 2002 . Despite the fact there are

several cell types in the prostate, nearly all of the prostate cancers are

adenocarcinoma, originating in the gland cells .

Liver cancer ranks as the sixth most common type of cancer world wide .Many

different liver related tumors are identified depending on the type of cells

where they originate, from these types about 83% are hepatocellular

carcinoma (HCC) that begin in the hepatocytes, the main type of liver cells.

Cervical cancer is the most common cause of cancer death among women in

developing countries and the second most common caner in women

worldwide. It is caused by a change in the epithelial cells, which

line the wall of the cervix, and the most common risk factor for this type

of cancer is the human Papillomavirus (HPV). In the last decades there were great advances in the diagnosis of cancer as well

as in the field of molecular oncology. However, the cure rate of most cancers

remains low. Several strategies have been used to cure cancer among which

the most common are surgery, chemotherapy, radiotherapy, and

immunotherapy. Other modern approaches such as hormonal and gene

therapy were proposed by researchers to replace conventional cancer therapy,

with variable degrees of success .

All of these therapies have undesired side effects, they are usually not

available all the time and they are expensive. For instance, in surgery

the immune system is compromised due to the large amount of cortisole

released subsequent to the surgery, which increase the probability of cancer

relapse .

Moreover, the current use of chemotherapy is accompanied with

difficult side effects. It inhibits bone marrow stem cells proliferation leading to

immune suppression . Radiotherapy which is widely used in the world is also

accompanied by a great deal of side effects. Lymphocytes are most readily

affected by radiation resulting in prolonged T-cell suppression . Other side

effects such as, bone necrosis, lung fibrosis, skin devascularization, ulceration,

nausea, vomiting, and renal damage are also associated with all types of

conventional therapies.

As the conventional cancer therapies failed to completely fulfill the criteria for

a successful cancer therapy, the use of naturally developed anticancer agents

has evolved as an alternative safe, low-cost and convenient one. Nontoxic

chemoprevention agents from natural resources were proposed by

researchers for this purpose.

II. Objectives The major scientific and technological progress in combinatorial chemistry,

drugs derived from natural products still make an enormous contribution to

drug discovery today. Efforts therefore are being made to identify naturally

occurring anti-carcinogenesis which would prevent, slow and/or reverse

the cancer induction and its subsequent development. Plants are good

reducing factors for cancer. This thesis deals with the anti-cancer benefit

of drug isolated from plant.

The aim of the current study is to investigate the effect of Solanum

viarum(Tropical Soda Apple), Acanthus illicifolious (Harkucha Kanta), Annona

squamosa(Custard Apple), Alstonia scholaris(Chatium) and Calotropis gigantea

(Akanda) leaf extracts on human breast cancer or blood cancer.

Specifically this study aims at:

1- Determination of the proliferation activities of each cell line in response to

each plant extract treatment.

2- Determination of percent viability of each cell line in response to each

plant extracts treatment.

3- Determination of any morphological changes of each cell line in each time

performing viability testing assay in parallel.

LITERATURE REVIEW

I. Conventional cancer therapy Despite the latest advances in medical sciences, and progress in strategies of

cancer treatment, cancer currently remains a tragic disease and is one of the

major causes of death worldwide. The principal methods of cancer treatment

include chemotherapy radiotherapy and surgery.

Chemotherapy is a systemic treatment, to which the whole body is exposed.

Among the most successful chemotherapeutic agent are Cisplatin, Mitomycin

and Docetaxel. All of these agents enhance serious side effects or long term

complication . These side effects include kidney damage, hearing

loose, lower blood count, liver damage, nerve damage, and blood vessel

damage.

External beams of Radiotherapy are associated with unacceptably high levels

of local-regional toxicity . Particularly, it affects the rapidly dividing cells of

mucosa, causing irritative urinary and blood loss . Later toxic effects result

from damage to the more slowly proliferating cells such as fibroblasts,

endothelial, or paranchymal stem cells causing chronic fibrosis and vascular

damage .

Other undesired side effects, such as, immune suppression, bone necrosis,

lung fibrosis and skin devascularization are seen with all types of

conventional therapies .

II. Plants with anticancer effects Plants are the chief source of natural products that are used in medicine. Even

Aspirin, the world best known and most universally used medication, has its

natural origins from the glycoside salicin which is found in many species of the

plant genera Salix and Populus .

The scientific literature is rich in epidemiological studies that support

significant differences in the occurrence of cancers between oriental

and occidental populations . Generally, populations that consume

a high level of natural herbal products have a reduced incidence of cancer.

An example is the low incidence of colon cancer in Asian countries with high

consumption of soybean products . Soy beans are the major dietary source of

saponins, which have been suggested as possible anticancer agents .

There is lately a great interest in screening for plants to be used in cancer

prevention and treatment. For this reason,leaf extracts from different plants

have been extensively studied and confirmed anticancer activity.

Studies that examined the therapeutic potential of plants leaf extracts

Plant Scientific Name Common Name Type of extraction Proposed active material

1. Solanum viarum Tropical Soda Apple Ether Solasodine glycoalkaloid

2. Acanthus illicifolious Harkucha Kanta Methanol Triterpenoids,Flavonoids,

Alkaloids

3. Annona squamosa Custard Apple Ethyl acetate Acetogenins,Alkaloids,

Dofamine

4 Alstonia scholaris. Chatium Methanol Alkaloids,Flavonoids

5. Calotropis gigantea Akanda Ethanol Triterpenoids,Flavonol

Glycosides

Selected Plants for leaf extract Scientific Name : Solanum viarum Dunal

Common Name : Tropical Soda Apple

Solanum viarum Dunal, belongs to the family Solanaceae, commonly called

Tropical Soda Apple (TSA) is a shallow rooted, profusely branched, perennial

shrub. It is native plant of Argentina and central Brazil (Mullahey et al, 1993)

and has been naturalized in many parts of the world including India. Solasodine

is a major glycoalkaloid constituent of this plant and it is a as the potential

alternative for diosgenin which share a characteristic conversion to 16-dehydro

pregnenolone acetate, the first step in steroid synthesis (Bhudavari, 1989).

Solasodine extracted from this plant is used as a steroid precursor to produce

contraceptive pills (Everist, 1981), treat cancer (Trouillas et al., 2005),

Addison's disease, rheumatic arthritis, chronic asthma, leukemia (Blood

cancer), obesity, palsy, skin diseases (Pingle and Dhyansagar, 1980), and anti-

inflammatory steroidal drugs

(Pandurangan et al., 2011).

Tropical soda apple plant(Solanum viarum)

Plant leafs Collection,Identification and extraction

The Tropical soda apple plant leafs was collected from Haldia river side area in

August,2015 and identified Botanical Survey of India,Botanical

Garden,Howrah-711103

Air dried plant leafs (100gm) were powdered in a mechanical grinder.

And the plant leafs powder were successively extracted by aquaous,

ether,ethanol,ethyl acetate, chloroform and methanol by using soxhlet

extraction apparatus. Used 1 gm powder for each exraction.

Then solvent was completely removed under reduced pressure and stored in

a vacuum dessicator. The yields of the ether,ethanol, chloroform and methanol

fraction were about 7.25% and 9.30 % respectively.

Qualitative analysis Preliminary qualitative analysis has been needed performed to know the

type of compounds present in the various extracts.

Further needed chemical group tests were performed for identified

salasodine glycoalkaloid , others and the yields of these ether,ethanol,

chloroform and methanol extracts were noted. These important contains

are functioning anti cancer activity in cancerous cell line.

Scientific Name : Acanthus ilicifolius Linn.

Common Name : Harkucha Kanta

Acanthus ilicifolius Linn. (Acanthaceae) a gregarious shrub, commonly found

with mangroves along the coastal regions of India. The common names of

Acanthus ilicifolius are Beng. Harkucha kanta, Eng. Holy leaved acanthus.

It is found commonly in the east and west coasts, also found in Meghalaya and

the Andamans. Leaves are simple, oblong to elliptic, varying in size, smaller in

flowering season.

Acanthus ilicifolius (Acanthaceae) has received considerable attention due to its

wide range of secondary metabolites and its traditional usage in Indian and

Chinese system of medicine. This plant is reported to be a mangrove.Mangrove

survives in the most hostile environment with fluctuating tidal and saline

regime. Hence, these plants are considered to be rich sources of

steroids,triterpenoids, saponins, flavonoids, alkaloids, and tannins.

The plant have demonstrated significant pharmacological activities like

antioxidant, anticarcinogenic, anti-osteporotic and hepatoprotective.

Traditionally, the plant has been used for dyspepsia, paralysis, asthsma,

headache, rheumatism, and skin diseases.

Harkuncha kanta Shrub(Acanthus ilicifolius)

Plant leaf Collection,Identification and extraction

The Harkucha Kanta Shrub leafs was collected from Haldia river side area in




And the plant leafs were successively extracted by aquaous,







type of compounds present in the various extracts


compounds like steroids,triterpenoids, saponins, flavonoids, alkaloids, and

tannins, of these ether,ethanol, chloroform and methanol extracts were

noted.These important contains are functioning anti cancer activity in

cancerous cell line.

Scientific Name : Annona squamosa Linn.

Common Name : Custard apple

Annona squamosa Linn. (Annonaceae), popular with common name of

“custurd apple or sugar apple”.

Its origin from West Indies and Central America. The plant is also cultivated

throughout the South Asia especially in tropical regions for edible purpose. It is

a small (about 5-6 m in height) deciduous tree with irregular branches.

Ethyl acetate extracts leaf of Annona squamosa L. were found

acetogenins,alkaloids,dofamine,salsolinol and Coclaurine. Its have significant

anticancer activity. It is effective remedy for various types of inflammatory

diseases as well as tumorous growths.

The plant has been used in traditional medicine of several tropical countries to

treat epilepsy, dysentery, cardiac problems, worm infection, constipation,

hemorrhage, antibacterial, dysurea, fever and ulcer. It also has anti-fertility

and abortifacient properties (Soni et al., 2012).

Custard apple tree(Annona squamosa Linn.)


The Custard apple tree leafs was collected from Haldia river side area in











type of compounds present in the various extracts.


compounds like acetogenins, alkaloids, dofamine, salsolinol and Coclaurine

of these ether, ethanol, chloroform and methanol extracts were noted.

These important contains are functioning anti cancer activity in cancerous

cell line.

Scientific Name : Alstonia scholaris Linn.

Common Name : Saptaparni or Chatium

Alstonia scholaris Linn. (Family Apocynaceae) which is popularly known as the

“Saptaparni” or “Devil’s tree”. Common name of Alstonia scholaris Linn. are

Bengali Chatium.

Alstonia scholaris Linn. is a medium to large tree. The upperside of the leaves

are glossy, while the underside is Greyish, its mature bark is grayish.

It is widely distributed in dried forests of India, Westwern Himalayas,Western

Ghats and in the Southern region.

The plant Alstonia scholaris has been used in different system of traditional

medication for the treatment of diseases and ailments of human beings. It is

reported to contain various alkaloids, flavonoids and phenolic acids. It has

been reported as anti-cancer, antioxidant, analgesic, anti-inflammatory, anti-

ulcer, bronchodilatory, antimicrobial, antiamoebic, antidiarrhoeal,

antiplasmodial, hepatoprotective, immunomodulatory, antiasthmatic, free

radical scavenging, anti-fertility and wound healing activities.

Saptaparni Chatium tree(Alstonia scholaris Linn.)


The Saptaparno or Chatium tree leafs was collected from Haldia river side area

in August,2015 and identified Botanical Survey of India,Botanical












compounds like alkaloids, flavonoids and phenolic acids of these

ether,ethanol, chloroform and methanol extracts were noted.These

important contains are functioning anti cancer activity in cancerous cell

line.

Scientific Name : Calotropis gigantea

Common Name : Akanda

Calotropis gigantea (Crown flower or Akanda) is a species of Calotropis native

to Cambodia, Indonesia, Malaysia, Philippines, Thailand, Sri Lanka, India, China,

Pakistan, Nepal, and tropical Africa.

It is a large shrub growing to 4 m (13 ft) tall. It has clusters of waxy flowers that

are either white or lavender in colour. The plant has oval, light green leaves

and milky stem.

Several phytochemicals have been isolated from Calotropis gigantea and they

include cytotoxic cardenolides, antifeedant nonprotein amino acid,

naphthaleneand terpene derivatives, flavonol glycosides, pregnanes, ursane-

type triterpenoids and steroids.

Traditionally extracts and preparations from roots and leaves of Calotropis

gigantea are used against abdominal tumours, boils, syphilis, tuberculous,

leprosy, skin diseases, piles, wounds, rheumatism and insect-bites.

Root bark of this plant is used in dysentery and as a purgative,

alterative,diaphoretic and emetic. Antipyretic, analgesic, anticonvulsant,

anxiolytic, sedative, hepatoprotective, wound healing, antidiabetic,

larvicidal,anti-inflammatory and anti-diarrhoeal activities of C. gigantea have

been scientifically proven.

Akanda shrub (Calotropis gigantean)


The Akanda shrub leafs was collected from Haldia river side area in













compounds like flavonol glycosides, pregnanes, triterpenoids and steroids of

these ether,ethanol, chloroform and methanol extracts were noted.These

important contains are functioning anti cancer activity in cancerous cell

line.

References 1. Chandra, V., and S. N. Srivastava. 1978. Solanum viarum Dunal

syn. Solanum khasianum Clarke, a crop for production of

solasadine. Indian Drug. 16: 53-60.

2. Nee, M. 1991. Synopsis of Solanum section Acanthophora: A group

of interest for glyco-alkaloides, pp. 258-266 In: J. G. Hawkes, R. N.

Lester, M. Nee and N. Estrada eds. Solanaceae III: Taxonomy,

chemistry, evolution. Royal Botanic Gardens Kew, Richmond,

Surrey, UK.

3. Khajure, P. V. & Rathod, J. L. (2011). Potential anticancer activity of

Acanthus ilicifolius extracted from the mangroves forest of Karwar,

west coast of India. World Journal of Science and Technology, 1(1),

1-6.

4. Wostmann, R. & Liebezeit, G. (2008). Chemical composition of the

mangrove holly Acanthus ilicifolius (Acanthaceae). Senckenbergiana

maritime, 38(1), 31-37

5. Neha Pandey and Dushyant Barve (2011). Phytochemical and

Pharmacological review on Annona squamosa Linn. International

Journal of Research in Pharmaceutical and Biomedical Sciences, 2(4):

1404- 1412.

6. Soni H, Malik SS and Singhai AK (2012). Evaluation of leaf of aqueous

extract of MeOH extract of Aannon squamosa on cell viability

American. J. Pharm. Tech. Res., 2(4): 936-944.

7. Abhijit Dey. .Alstonia scholaris R.Br. (Apocynaceae): Phytochemistry

and pharmacology: A concise review.Journal of Applied

Pharmaceutical Science. 2011;01(06): 51-57.

8. Arulmozhi S, Papiya Mitra Mazumder, Sathiya Narayanan L, Prasad

A Thakurdesai. In vitro antioxidant and free radical scavenging

activity of fractions from Alstonia Scholaris linn. R.Br. International

Journal of PharmTech Research. 2010; 2(1):18-25.

9. Sen S, Sahu NP, Mahato SB. Flavonol glycosides from Calotropis

gigantea. Phytochemistry 1992; 31: 2919-2921.

10. Kintzios SE. Terrestrial plant derived anticancer agents and plants

used in anticancer research. Crit Rev Plant Sci 2006; 25: 79-113.

Anti cancer thesis

Health & Medicine

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