Chaemoprevention of cancer using dietary

phytochemicals

BY- AWANTIKA SINGH

INTRODUCTION

Cancer is a growing health problem around the world(particularly with the steady rise in life expectancy, increasing urbanization and the subsequent changes in environmental conditions, including lifestyle)

Even with advances in medical science disciplines such as surgery, radiotherapy and chemotherapy, there is still no significant progress in its treatment.

Conventional cancer therapies evoke severe side effects and in many cases, patients recover from cancer and die due to organ failure and immunosuppression.

According to a recent report by the World Health Organization (WHO), there are now more than 10 million cases of cancer per year worldwide.

It has been estimated that 10–70% (average 35%) of human cancer mortality is attributable to diet. Their observations, which are based on statistical and epidemiological data, mainly concerned dietary factors that increase risk called as suspected human carcinogens.

So, the increased incidence of cancer in the world today justifies the application of phytochemical chemoprevention.

DIRTARY PHYTOCHEMICAL

Phytochemicals are natural occurring, non-nutritive biologically active chemical compounds in plants.

It act as a natural defence system for host plants and provide colour, aroma and flavour.

Phytochemicals are a potential alternative source of safer chemicals with anticarcinogenic effects and antimutagenic properties

.IMPORTANCE OF PLANT DERIVED CHEMICALS: More than 250 population-based studies, indicate that

people who eat about five servings of fruit and vegetables a day have approximately half the risk of developing cancer ,of those who eat fewer than two servings.

They are found as a substance responsible for the health promoting properties of varieties of natural and functional foods due to their ability to alter cell communication, and DNA repair and influence cell processes that can cause development of cancer and other diseases

The induction of apoptosis in a neoplastic cell without damaging the healthy cells of the body with phytochemical chemopreventive agents seems to be the best strategy in cancer management and treatment .

It can Inhibit cancer initiation and prevent carcinogenic agents from reaching the targeted site &decrease tissue vulnerability,preventing targeted tissues from receiving carcinogenic stimuli.

It can also stop malignant proliferation of initiated cells in both promotion and progression stages of cancer transformation.

phytochemicals can be of 2 types

Blocking agents are substances like indole-3-carbinol,sulforaphane

and flavonoids which avert cancer causing agents from accomplishing their effects on the normal cells, inhibit their metabolic stimulation, and also enhance their detoxification.

Suppressing agents They function by interfering with the promotion

and progression of carcinogenesis through their effect on cell proliferation, integration and programmed cell death which inhibits translation of initiated cells to form cancerous celL

CLASSES OF PHYTOCHEMICALS AND THEIR SOURCES

Blocking agents

Suppressing agents

o carotenoids,

o phenolics,

o alkaloids,

o organosulphur compounds

CAROTENOIDS: include β-carotene,lycopene, zeaxanthin and

lutein. Their sources include carrots, tomatoes, sweet potatoes, broccoli and spinach.

PHENOLICS A secondary metabolites that are vital for plant

growth and reproduction, and also serve as defence against pathogens, and predators that attack plants. They have been found useful in humans for lowering the effect of cancer andother chronic diseases. Phenolics possess an aromatic ring and hydroxyl groups and include phenolic acids, flavonoids stilbenes, coumarinsand tannins. Their primary sources arevegetables, grapes, fruits, pineapple, banana and green tea.flavonoids - A phenolic compounds that have antioxidant properties; examples include flavonal (querectin), flavones (apigenin), flavanols (epigallocatechin gallate) and isoflavonoids (genistein) (Hollman and Arts, 2000). Phenolic acids include resveratrol, curcumin, caffeic and ferulic acid .

ALKALOIDS are natural product that contains heterocyclic

nitrogen atoms, are basic in character. And anticancer actions -dimeric indoles,vincristine, vinblastine.

ORGANOSULPHUR COMPOUNDS which include sulforaphane, diallyl sulphide, and

indole-3-carbinol and s-allyl cysteine. Their dietary sources are onion, broccoli, garlic, an.d cruciferous vegetables

• Cancer is generally recognized as a multistep process in which distinct molecular and cellular alterations occur. The main stages of carcinognenesis is:

initiation, promotion progression

Chemopreventive phytochemicals can block or reverse the premalignant stage (initiation and promotion) of multistep carcinogenesis. They can also halt or at least retard the development and progression of precancerous cells into malignant one.

One of the central components of the intracellularsignalling network that maintains homeostasis is the family of proline-directed serine/threonine kinases -the mitogen-activated protein kinases (MAPKs).Abnormal or improper activation or silencing of the MAPK pathway or its downstream transcription factors can result in uncontrolled cell growth, leading to malignant transformation. Some phytochemicals‘switch on’ or ‘turn off ’ the specific signalling molecule(depending on the nature of the signalling cascade they target, preventing abnormal cell proliferation and growth. Cell-signalling kinases other than MAPKs, such as protein kinase C (PKC) and phosphatidylinositol-3-kinase (PI3K), are also important targets of certain chemopreventive phytochemicals. These upstream kinases activate a distinct set of transcription factors, including nuclear factor κB (NF-κB) and activator protein 1.There are some of the examples of phytochemicals :-

Mechanisms of chemoprevention

Cellular signaling molecules as targets:

MOLECULAR TARGETS OF PHYTOCHEMICALS

Diagram showing the activity of blocking agents and supressing agents obtained from dietary

plants

diferuloylmethane or 1,7bis(4hydroxy3methoxylphenyl)-1,6-heptadiene-3,5-dione) is a derivative of turmeric . curcumin has a distinctive number of health-promoting properties suchas anticarcinogenic,anti-inflammation,antioxidative and antimutagenic activities in humans

This is a phenolic compound that shows distinctive flavour of ginger. It inhibits cell

developmental factor induced by AP1 stimulation and transcription to cancer formation .

Is a polyphenol compound seen mostly in green tea which has great anti-proliferation and anticancerous effects . It also inhibits Ras-activated AP1 activity.

This is seen in pepper. It has distinctive pungent characteristics. It induces apoptosis.

GENISTEIN: an isoflavone and is a dietary component of soybeans. It plays

important roles in lowering occurrence of breast and prostate cancer. Increased consumption of genistein in the diet controls cancer expression, tyrosine kinase regulated proteins, and insulin growth factor receptor.

RESVERATROL (3, 4’, 5-trihydroxytransstibene) is a polyphenol abundantly seen in

grapes . It inhibits PKC stimulation, and AP1 transformational changes. It also induces normal cell death and reduces stimulation of NF-kB in human pancreatic carcinoma cell lines.

ELLAGIC ACID (2,3,7,8-terahydroxychromeno[5,4,3-cde] chromene-5,10-dione) is a

polyphenol compound seen abundantly in many fruits . It has antioxidant properties and causes inhibition of cancer proliferation by controlling the activities of the cell cycle and activates normal cell death.

Curcumin,

Gingerol

Epigallocatechin gallate (EGCG):

Capsaicin:

(3, 3’, 4’, 5, 7-pentahydroxyflavone) is a flavonol seen

mostly in tea, apple and onion. It has anti-oxidant properties and also serves as an anti-inflammatory agent. Research has shown that it has potential for arresting the cell cycle in cancer and also induces caspase dependent apoptosis . It also prevents normal cells from forming cancerous cells.

Sulforaphane

is an isothiocynanate present in cruciferous vegetables like broccoli that has capacity to activate phase 2 detoxification enzymes. It has been observed that sulforaphane may associate with reduced glutathione and reduction-oxidation controllers like thio redox

Quercetin

Mechanism of action of phytochemical chemopreventive

agents on NF-kB and AP1

Transcriptional activation by NRF2

Benefits and limitations ofphytochemicals in Chemoprevention

Most modern medicines currently used for treatment of cancer are not only very toxic, but are expensive in management of the disease recent research has indicated that consistent eating of whole fruits, vegetables and grain in our daily diets can minimise the risk of cancer diseases.

These edible foods containing phytochemicals are essential to ensure a healthier population that has low incidence of cancer.

These phytochemicals are inexpensive, effective, readily applicable and accessible bioactive compounds that neutralise free radicals that causes cell damage.

• They also inhibit cellular oxygenase,pro-inflammatory responses and nitric oxide production and induce apoptosis with increased neuroprotective effects

Phytochemicals in cancer chemoprevention are considered as the cheapest option incancer treatment.

Iimitation: bioavailability . digestibility of these natural compounds in the

body. time consuming involves much expense during its clinical trials.

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