Roll. no. 14423

By. Awantika Singh, Dr. Nilima kumari

Secondary Metabolites As Anti cancer Agents

Natural occurring, non-nutritive biologically active compounds in plants. Plant secondary metabolites are the products of secondary metabolism. A common role of secondary metabolites in plants is Defense

Mechanism. These are used to fight off herbivores, pests and pathogens . Used as flavorings, dyes and pigments, pesticides and food additives

(Nobili et al, 2009).

CANCER: Cancer is a growing health problem around the world due to life

expectancy, increasing urbanization ,changes in environmental conditions. 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 even if Patients recover from cancer, die due to organ failure and immunosuppression.( Surh, 2003)

So, we need more natural and more health promoting properties.

Secondary metabolites

Secondary Metabolites As Anti Cancer Agents

Anti mutagenic and anti carcinogenic properties.

Inhibit, reverse or retard tumorigenesis.

Interfere with processes involved tumor formation, such as suppression of NF-kB and AP1 activation.

Target xenobiotic metabolizing enzymes, reactive oxygen species, inflammation, cell cycle, apoptosis, invasion, angiogenesis, transcription factors, and protein-kinases.

Able to alter cell communication, and DNA repair and influence cell processes that can cause development of cancer and other diseases.

Decrease tissue vulnerability, prevent targeted tissues from receiving carcinogenic stimuli.

Classification of secondary metabolites

Phenols TerpenoidsAlkaloids &

Organosulphur compounds

PHENOLS

These are one aromatic ring compound with one or more hydroxyl groups attached with it. It ranges from simple, low molecular-weight, single aromatic-ringed compounds to large and

complex.

Flavonoids are polyphenolic compounds ( 15 carbons) with two aromatic rings connected by a three-carbon bridge.

UV protection, pigmentation, disease resistance in plant. Non-flavonoids can be Phenolic acids, Hydroxycinammates, stilbenes. Resveratrol is the most common stilbene, Hydroxycinnamates are p-coumaric, caffeic and ferulic

acids.

PHENOLS

Flavanoid

Non flavanoid CAFFEIC ACID CAPE

RESVERATOL

TERPENOIDS

Terpenoids are the hydrocarbons of the general formula (C5H8)n Volatile substances which give plants and flowers their fragrance. They function as phytoalexins in plant defense. Some compound have interesting anti cancer activity.

TERPENOIDS

Hemiterpenoids,

Monoterpenoids,

Sesquiterpenoids

Diterpenoids,

Sesterterpenoids

Triterpenoids,

Tetraterpenoids

Polyterpenoid

D-LIMONINECAROTENE

LYCOPENE POLYPHENOLS

Alkaloids

Nitrogen containing substances. The structures of alkaloids are usually mimicked in synthesis of chemical

drugs. Vinblastine and vincristine are the first significant anticancer alkaloids .

ALKALOIDS

True alkaloids

Proto Alkaloids

Polyamine alkaloids

Peptide and cyclopeptide

Pseudo alkaloids

VINCRISTINE

TAXOL

CAMPTOTHECIN

Oraganosulphur COMPOUNDS:

Sulphur containg compounds. Voletile , have acrid taste They are mainly for defense mechanism in plants It exhibits Antibacterial ,Antifungal, Antiviral, and antiprotozoal activity..

ORGANO SULPHUR

GLUCOSINOLATE

ALLICINS

THIOPENE

ALLICINSTHIOPENE

GLUCOSINOLATE

Some of secondary metabolites USED IN cancer Vinblastin and vincristine in leukemias, lymphomas, advanced

testicular cancer, breast and lung cancer and Kaposi`s sarcoma Taxol ovarian cancer, advanced breast cancer, and lung

cancer. Camptothecin are used to treat ovarian, colorectal, and small-

cell lung cancers, Berberine - against colon tumor formation. It plays a key role in

colon tumorigenesis. Sulforaphane can inhibits chemically induced Kaposi`s

sarcoma in rats. D-limonene inhibits the progression of mammary tumors

induced in rats. Genistein : plays important roles in lowering occurrence of

breast and prostate cancer

MECHANISMS OF SECONDARY METABOLITES IN CANCER

According to the activity in prevention of cancer, Secondary metabolites can be of three type .( stoner et al, 1997)

Cancer

Inhibitors of carcinogen formation

Blocking agents

Suppressing

agents

Inhibitors of carcinogen formation:

Inhibit th the formation of nitrosamine from secondary amines and nitrite in the stomach, leads to affects lung tumor in mice in laboratory.

Caffeic acid, ferulic acid, gallic acid , sulfhydryl compound .vitamins C and E, phenolic compounds.

It ca n be included into the diet where suspected high rate of endogenous formation of nitrosamine

GALLIC ACID GALIC ACID

FERULIC ACID

EGCG

Blocking agents:

Blocking agent interfare with intiation stage of carcinogenesis. Procarcinogen must be activated to damage DNA and Mutation in precancerous cell . On this

basis , blocking agents can be of following types : Inhibitors of Cytochrome P450 Enzymes: by

isothiocynate ,diallyl ,sulfide (Allium vegetables), Ellagic acid . Inducers of Cytochrome P450 Enzymes: Sulforaphane. Scavengers of Electrophiles, Free Radicals : react with the activated

(electrophilic) forms oand ros simply trap or scavenge the electrophils. Inducers Of DNA Repair The antioxidant properties for e.g.,

LYCOPENEINDOL-3-CARBINOL

POLYPHENOLS

DIALLYL SULFIDE ELLAGIC ACID

Supressing Agents

In the promotion and progression of carcinogenesis. Effect on cell proliferation, integration and apoptosis which inhibits translation of

initiated cells to form cancerous cells. They can be of following types :

Inhibitors of polyamine metabolism: the suicide inhibitor of ODC, α-difluoromethylornithine (DFMO). Ornithine Decarboxylase (ODC) is the key enzyme in the biosynthesis of polyamine. DFMO inhibits tumorigenesis.

Inducers of Terminal Cell Differentiation: Vitamin A and retinoids capable restoring the ability of abnormally proliferating cells.

Modulators of Signal Transduction molecule : Protein kinase C (PKC) phosphatidylinositol 3 kinase (PI3K), nuclear factor κB (NF-κB), activator protein 1 (AP1).

Modulaors of Growth Factor Activity inhibit the oncogenic activity of tumours related to ras gene. : D-limonene,

capsaicin Gingerol

Future prospects and conclusion

Inexpensive, readily applicable and accessible.(Surh, 2003) People who takes five serving of colurful fruits a day have lesser extent of

cancer than to those who takes only two serving of fruits a day. Curcumin, Neem Limonoids, Lycopene: have anticarcinogenic, anti-

inflammation, antioxidative and antimutagenic activities, Garlic and its organosulfur constituents enhance carcinogen

detoxification and immunity , ROS scavenging, suppressing proliferation, angiogenesis and inflammation, inducing apoptosis and DNA repair.

Black tea , ECGC: Improve oxidative stress and inhibit tumor invasion and angiogenesis

Capsaicin, Quercetin : induces apoptosis. Genistein: inhibit nuclear translocation of NF-kB. Gingerol, Resveratrol: inhibits AP1 stimulation. Sulforaphane: has capacity to activate phase 2 detoxification enzymes. Camptothecin (CPT) inhibits the DNA enzyme topoisomerase I (topo I). Salvicine triterpenoids ,carotenoids have ablity to overcome multi drug

resistance.

so, ensure a healthier population that has low incidence of cancer , can be used as a component of anti cancer agents .