INTRODUCTION:

Natural products especially plants have been used for the treatment of various diseases for thousands of years. Terrestrial plants have been used as medicines in Egypt, China, India and Greece from ancient times and an impressive number of modern drugs have been develop from the first written record on medicinal uses of plants appeared in about 2600 BC from the Sumerians and Acadians. Among the human disease’s cancer is one, probably the most important genetic disease which can be treated with medicinal plants. Every year millions of people are diagnosed with cancer, leading to death. In majority of the cases cancer is the abnormal growth of cell in our bodies that can lead to death. Cancer cell usually invade and destroy normal cells. These cells are born due to imbalance in the body and by correcting this imbalance, the cancer may be treated.

Billions of dollars have been spent on cancer research and yet we do not understand exactly what cancer is. Every year millions of people are diagnosed with cancer leading to death.

Cancer disease caused by an uncontrolled division of abnormal cells in the part of the body. The cancer is very serious if the tumor begins to spread throughout the body. These are many different types of cancer. They are named based on where the tumor is located, or where it first started growing in the body. The most common forms of cancer are colon, lungs, breast and prostate cancer. Chemotherapy is the use of anticancer drugs. Anticancer drugs destroy cancer cells by stopping growth or multiplication at some point in their life cycles. Drugs may be administered intravenously, orally, by injection into muscles, topically or in other ways, depending on the DRUG and the type of cancer. Chemotherapy is often given in cycle of alternating treatment and rest periods. Radiation therapy is the treatment of cancer and other diseases with ionizing radiation. Ionizing radiation destroy cells or genetic material of cells in area being treated, thereby making it impossible for these cells to continue to grow.

The search for anticancer agents from plant sources stated in earnest in the 1950s with the discovery and development of the Vince alkaloids, vinblastine, vincristine and the isolation of the cytotoxic podophyllotoxines, as a result The United States National Cancer Institute (NCI) initiated an extensive plant collection programs in 1960 focused mainly in temperate regions. This led to the discovery of many novel chemo types showing a range of cytotoxic activities (Cassady and Douro’s 1980), including the taxanes and camptothecines, but their development into clinically active agents spanned a period of some 30 years from the early 1960s to 1990s. The plant collection programs were terminated in 1982 but development of new screening technologies led to the revival of collection of plants and other organisms in 1986, with a focus on the tropical and subtropical regions of the world. It is interesting to note, however that no new plant derived clinical anticancer agents have, as yet, reached the stage of general use, but a number of agents are in preclinical development.

Importance of Herbal Medicines in Cancer:

Cancer is a general term applied of series of malignant diseases that may affect different parts of body. These diseases are characterized by a rapid and uncontrolled formation of abnormal cells, which may mass together to form a growth or tumor, or proliferate throughout the body, initiating abnormal growth at other sites. If the process is not arrested, it may progress until it causes the death of the organism. The main forms of treatment for advance stage cancer in humans are surgery, radiation and drugs (cancer chemotherapeutic agents). Cancer chemo-therapeutic agents can often provide temporary relief of symptoms, prolongation of life, and occasionally cures. Many hundreds of chemical variants of known class of cancer chemotherapeutic agents have been synthesized but have a more side effect. A successful anticancer drug should kill or incapacitate cancer cells without causing excessive damage to normal cells. This ideal is difficult, or perhaps impossible, to attain and is why cancer patients frequently suffer unpleasant side effects when under-going treatment. Synthesis of modifications of known drug continues as an important aspect of research. However, a waste amount of synthetic work has given relatively small improvements over the prototype drugs. There is a continued need for new prototype-new templates to use in the design of potential chemotherapeutic agents: natural products are providing such templates. Recent studies of tumor-inhibiting compound of plant origin have yielded an impressive array of novel structures. Many of these structures are extremely complex, and it is most unlikely that such compounds would have been synthesized in empirical approaches to new drugs.

Nowadays, various methods are used for cancer treatment such as chemotherapy, but in this method, because of non selectivity of medicines, a high percentage of healthy cells will be lost with cancer cells. The most important problem in cancer treatment is destroying tumor cells in the presence of natural cells, without damaging natural cells. In order to prepare anticancer medicines from natural resources like plants, testing cytotoxic compounds and screening raw extracts of plants is necessary. Therefore, availability of natural products with higher effectiveness and lower side effects is desired. Medicinal herbs are important for cancer treatment due to their multiple chemical compounds for discovering new active materials against cancer. Plants produce a wide range of chemical compounds that apparently have no direct role in the plants’ growth. These compounds are called secondary metabolite. Alkaloids, terpenoids, Flavonoids, pigments, and tannins are important constituents of these compounds. Secondary metabolites have biologic effects such as anti-inflammatory, anticancer, contraceptive, and different effects on hematopoietic cells, lipids, and cardiovascular systems. Different improvements are reported in common treatments of cancer by finding secondary compounds of natural products and medicinal herbs. It is believed that anticancer effects of plants develop by suppressing cancer’s stimulating enzymes, repairing DNA, stimulating production of antitumor enzymes in cell, increasing body immunity, and inducing antioxidant effects. Cancer is a painful disease and fighting against this disease is very important for public health. Regarding the fast progress in the phytochemical study of herbal products, plants are transforming to popular anticancer sources. In cancer, initial tumors will be treated by chemical supplement therapies or surgery. But cancers in the metastasis stage will resist against care. But in chemotherapy, due to non selectivity of used medicines, a high percentage of healthy cells will be destroyed with cancer cells. Nowadays, more than 60% of anticancer compounds that are useful for cancer patients are obtained from herbal, marine, and microorganism sources. The positive effect of plants in cancer treatment has been studied extensively and has shown positive results. Also, different researches and studies have proved the positive effect of plants in curing diabetes, fertility and sterility, thyroid disorders, anemia, and psychological disorder. Finding plants that replace chemotherapy and cumbersome cures of cancer with cytotoxic effects is necessary.

Cancer and Its Classification:

Ayurvedic Concept of Cancer:

Charaka and Sushruta Samhita both described the equivalent of cancer as “granthi” and “arbuda”^. “Granthi” and “Arbuda” can be inflammatory or devoid of inflammation, based on the doshas involved. Three doshas “Vata, Pitta and Kapha” in body are responsible for disease and the balanced coordination of these doshas in body, mind and consciousness is the Ayurvedic definition of health. Tridoshicarbudas are usually malignant because all three major body humors lose mutual coordination, resulting in a morbid condition. Neoplasm can be classified in Ayurveda depends upon various clinical symptoms in relation to tridoshas.

Group I:

Diseases that can be named as clear malignancies, including arbuda and granthi, such as mamsarbuda (sarcomas) and raktarbuda (leukemia), mukharbuda (oral cancer), and asadhya vrana (incurable or malignant ulcers).

Group II:

Diseases that are not cancers but can be considered probable malignancies, such as ulcers and growths. Examples of these are mamsaja oshtharoga (growth of lips), asadhya galganda (incurable thyroid tumour), tridosaja gulmas, and asadhya udara roga, (abdominal tumours like carcinomas of the stomach and liver or lymphomas).

Group III:

Diseases in which there is a possibility of malignancy, such as visarpa, asadhya kamala (incurable jaundice), asadhya pradara (intreatable sinusitis).

Causes of Cancer:

Modern medicine attributes most cases of cancer to changes in DNA that reduce or eliminate the normal controls over cellular growth, maturation, and programmed cell death. These changes are more likely to occur in people with certain genetic backgrounds and in persons infected by chronic viruses (e.g., viral hepatitis may lead to liver cancer; HIV may lead to lymphoma). The ultimate cause, regardless of genetic propensity or viruses that may influence the risk of the cancer, is often exposure to carcinogenic chemicals (including those found in nature) and/or to radiation (including natural cosmic and earthly radiation), coupled with a failure of the immune system to eliminate the cancer cells at an early stage in their multiplication. The immunological weakness might arise years after the exposure to chemicals or radiation. Other factors such as tobacco smoking, alcohol consumption, excess use of caffeine and other drugs, sunshine, infections from such oncogenic virus, like cervical papilloma viruses, adenoviruses Karposis sarcoma or exposure to asbestos. These obviously are implicated as causal agents of mammalian cancers.

Environmental factors which, from a scientist’s standpoint, include smoking, diet, and infectious diseases as well as chemicals and radiation in our homes and workplace along with trace levels of pollutants in food, drinking water and in air. Other factors which are more likely to affect are tobacco use, unhealthy diet, not enough physical activity, however the degree of risk from pollutants depends on the concentration, intensity and exposure. The cancer risk becomes highly increased where workers are exposed to ionizing radiation, carcinomas chemicals, certain metals and some other specific substances even exposed at low levels. Passive tobacco smoke manifold increases the risk in a large population who do not smoke but exposed to exhaled smoke of smokers_.If the process is not arrested it may progress until it causes the death of organisms. The

Types of Cancer:

1. Cancer of blood and lymphatic systems:

· Hodgkin's disease

· Leukemia's

· Lymphomas

· Multiple Myeloma

· Waldenstrom's diseases

2. Skin cancer:

· Malignant melanoma

3. Cancer of digestive system:

· Esophageal cancer

· Stomach cancer

· Cancer of pancreas

· Liver cancer

· Colon and Rectal cancer

· Anal cancer

4. Cancer of urinary system:

· Kidney cancer

· Bladder cancer

· Testis cancer

· Prostate cancer

5. Cancer in women:

· Breast cancer

· Ovarian cancer

· Gynecological cancer

· Adenocarcinoma

· Choricarcinoma

6. Miscellaneous cancer:

· Brain cancer

· Bone cancer

· Characinoid cancer

· Nasopharyngeal Cancer

· Retro peritoneal sardines

· Soft tissue cancer

· Thyroid cancer

Herbal Drugs use in Cancer Treatment:

Medicinal plants play a significant role as therapeutics aids in health system in all over the world. Therefore, from ancient period to modern era herbal drug have been used to cure several diseases. The medicinal value of these plants lies in some chemical substances that produce a definite physiological action on the human body. These medicinal plants constitute an important group of non wood forest products and represent a vast potential source for anticancer compounds. Approximately 80% of the world population uses plants as a source of medicine for healthcare. India has been one of the pioneers in the development and practice of well documented indigenous system of medicine, particularly in Ayurveda, Siddha, and Unani system, all these systems of medicine are gaining world wild popularity according to WHO essential medicine list contain 252 drugs out of which 11% is exclusively of plant origin. Consequently, there has been great demand for these plants but regrettably only a few medicinal plants are been cultivated on a commercial scale with a majority steel being collected from the wild. Due of over exploitation of plant from the wild the habitat destruction several medicinal plants have become endangered. For survival there is need to conserve the wild population plant in natural or wild condition to meet the commercial needs through cultivation. in the present scenario herbal medicine are in evolutionary process for developing new medicines there four pharmaceutical companies are involved in research on plant material for their potential medicinal value as the demand for herbal products is growing exponentially due to its fewer side effects as compare to other system of medicine. According to world health organization cancer is the second most frequent cause of death in developed countries. Many cancer patients use complementary and alternative medicine treatments. A wide range of knowledge regarding pharmacological research has considerably improve the quality of herbal drug in cancer treatment. Among several treatments’ homeopathy is one of the most popular complementary and alternative medicine modalities for cancer patients but due to the lack of knowledge about its utilization, is a major factor for threatening the large-scale cultivation of plant. In this review we tried to summaries some medicinal plant species information which may be used to open a new era for development of new drug for various ailments. Some important well-known Phytochemicals used for the treatment of cancer are listed below.

Herbal anticancer drugs:

1. Vinca.

2. Podophyllum.

3. Taxus

4. Hemp

1. Vinca:

1.1 Description of Catharanthus roseus

1.1.1 Taxonomical Description:

Kingdom: Plantae

Order: Gentianales

Family: Apocynaceae

Genus: Catharanthus

Species: Roseus

Botanical Name: Catharanthus roseus

1.1.2 Geographical distribution:

Native of Madagascar abundantly neutralized in many regions particularly in arid coastal location. Being cultivated of hundreds of year’s C. roseus is evergreen perennial sub shrub with height of 30cm. to 1m. Cultivated as ornamental plant almost throughout the tropical and subtropical world^.

1.1.3 Botanical description:

The leaves are green, root is pale grey, and flowers are violet pink- white or carmine- red in color. The odour is characteristic and taste is bitter. Vinca is an erect, pubescent herb, with branched tap-root. Leaves are simple, petiolate, ovate, or oblong, unicostate, reticulate, entire, brittle with acute apex and glossy appearance. Flowers are bractate, pedicellate, complete, hermaphrodite, normally 2-3cm in cymoseaxillary clusters. Fruits are follicles with several black seeds.

1.2 Phytoconstituents:

The major constituents present in Catharanthus roseus are given below with their structure:

Table 2: Vinca alkaloids

Sr. No.	Name
1	Vinblastine
2	Vincristine
3	Vinorelbine
4	Vindesine

1.3.1 Ethno medicinal Use:

C. roseus has been used since long times for the treatment of various diseases in different parts of the world. It was used as diuretic, astringent and to treat cough, nose bleed, sore throat, mouth ulcer and bleeding gums. It was used to get relief lung congestion and inflammation and to treat diabetes.

1.3.2 Pharmacological Use:

Antibacterial activity: The crude extract from different parts of catharanthus roseus against several bacteria’s. C. roseus provides broad spectrum resistance against microbial agents in the treatment of number of diseases. It has proved to posses efficient anti-viral, anti-bacterial and anti-fungal compound. Antidiabetic, hypolipidemic, malaria, dementia, etc can also be treated by using the different extracts of these plants. C. roseus has the ability to improve the blood supply to brain which results in increase supply of oxygen and glucose to brain and also preventing the abnormal coagulation of blood. these plants increase the insulin production and utilization of sugar from food which helps in curing diabetes. C. roseus also helps to increase the level of serotonin. Phenolic compounds are the products of secondary metabolisms of plants and acts as a anti-oxidants, anti-inflammatory, anti-microbial, cardio protective and anti-allergic agents.

Anticancer activity:

The division of cancer cell is interfere by these drugs along with their derivatives such as vinflunine, vincristine in the treatment of leukemia in children and vinblastine for Choricarcinoma and Hodgkin’s diseases.

1.4 Mechanism of action:

Vinca alkaloid belongs to an important class of anticancer drugs. The mechanism of action of vinca alkaloids is that they inhibit the cell proliferation by affecting the micro tubular dynamics during mitosis, and this causes a characteristic block during mitosis leading to apoptosis. Vinblastine can cause side effect including bone pain, depression, dizziness, constipation, hair loss, stomach pain and loss of appetite. Microtubule disruptive drugs like vinblastine, colcemid, nocodazole have been reported to act by two mechanisms. At very low concentrations they suppress microtubule dynamics and at higher concentrations they reduce microtubule polymer mass polymer mass. Vinblastine is an anti-cancer medication prescribed in various cancers such as Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, breast cancer, testicular cancer, mycosis fungoides, Kaposi's sarcoma related to acquired immunodeficiency syndrome (AIDS), Letterer-Siwe disease. Vinblastine is also used to treat non-small cell lung cancer, bladder cancer, head and neck cancer, cervical cancer, idiopathic thrombocytopenia purpura, and autoimmune hemolytic anemia. It is amitotic inhibitor, and is used in cancer chemotherapy. Vincristine is created by the coupling of indole alkaloids vindoline and catharanthine in the vinca plant. Tubulin is a structural protein that polymerizes to microtubules. The cell cytoskeleton and mitotic spindle, among other things, are made of microtubules. Vincristine binds totubulin dimers, inhibiting assembly of microtubule structures. Disruption of the microtubules arrests mitosis in metaphase. Therefore, the vinca alkaloids affect all rapidly dividing cell types including cancer cells, but also those of intestinal epithelium and bone marrow. The main side-effects of vincristine are peripheral neuropathy, hyponatraemia. Its main uses are in non-Hodgkin's lymphoma, Hodgkin's lymphoma, chemotherapy regimen, in acute lymphoblastic leukemia, and in treatment for nephroblastoma (Wilms tumor, a kidney tumor most common in young children). It is used in combination with prednisone to treat childhood leukemia_.

Table 3: Use of Phytoconstituents

Sr. No.	Analogues	Therapeutic use
1	Vinblastine	Hodgkin’s diseases, Testicular germ cell cancer
2	Vincristine	Leukemia, Lymphomas
3	Vinorelbine	Solid Tumour, Lymphomas, Lung cancer
4	Vinflunine	Bladder cancer, Breast cancer

2. Podophyllum:

2.1 Description of Podophyllum hexandrum

2.1.1Taxonomical Description:

Kingdom: Plantae

Order: Ranuculales

Family: Berberidaceae

Genus: Podophyllum

Species: hexandrum

Botanical Name: Podophyllum hexandrum_.

2.1.2 Geographical distribution:

Podophyllum hexandrum is native to the lower elevations of Himalayan region. It grown in Himalayan regions in very restricted locations of Zaskar, Suru valleys of Ladakh, Kashmir region in Jammu and Kashmir, Lahaul, Spiti, Kangra, Chamba and Kinnaur im Himachal Pradesh, in Kumaon and garhwal in Utterakhand, Sikkim and Arunachal Pradesh

2.1.3 Botanical description:

Podophyllum hexandrum an erect perennial herb 15- 40 cm tall. It is low to the ground with a glossy green, grand nodule rhizome with many adventitious roots. 2-3 umbrella like, lobed leaves arise on its few stiff branches, they completely unfurl after the plant has bloomed and are dark green splotched with brown. The name Podophyllum is taken from podos meaning a foot, and phyllon which means a leaf. White or pale pink six petaled flower are borne at the end of stouts stem; these are followed by freshly, oval red barriers. Leaves are rounded in outline, 10-25 cm long, deeply cut into 3 ovate, toothed lobes, sometimes further lobed. Fruit is a large scarlet or reddish berry with many seeds embedded in pulp^.

2.2 Phytoconstituents:

Active constituents of Podophyllum hexandrum root of the plant has been reported to possess 56% podophyllotoxines content. Podophyllum hexandrum also contain a number of compounds with significant pharmacological properties which are given below:

Table 5: Podophyllum Phytoconstituents

Sr. No.	Names
1	Podophyllotoxines
2	Etoposide
3	Teniposide

2.3 Uses:

2.3.1 Ethno medicinal use:

Podophyllum hexandrum rhizomes have a long medicinal history among native north American tribes who used rhizomes powder as a laxative or anthelmintic. A poultice of powder was also used to treat warts and timorous growth on the skin. In Kashmir it has been used in traditional system of medicine from time immemorial and is locally known as Banwangun. Indian Podophyllum has long history of usage amongst native of the Himalayas, an aqueous extract of root being a common cathartic. It has also been used as a remedy in ophthalmic. Traditional use of Podophyllum hexandrum in the treatment of colds, constipation, septic wounds, burning sensation, plague, allergy, inflammatory condition of the skin, cancer of bladder and lungs, leukemia, lymphoma.

2.3.2 Pharmacological use:

Podophyllotoxines is a natural plant secondary metabolite mainly existed in the root of P. hexandrum and as well as its congeners and derivatives has pronounced biological activity mainly as anticancer, antineoplastic and anti-HIV drugs, etc. Podophyllotoxines is a naturally occurring lignan which is gifted with potent cytotoxicity. It acts as a mitotic spindle poison, binding the microtubules and causing mitotic arrest in metaphase. The application of podophyllotoxines cured almost all the warts completely in less time than other strategies and with fewer side effects. Podophyllotoxines and analog compounds are also active against cytomegalovirus and Sindbis virus. Podophyllotoxines is also effective in the treatment of anogenital warts in children and against Molluscum contagiosum, which is generally a self-limiting benign skin disease that affects mostly children, young adults, and HIV patients. Podophyllotoxines has other uses in dermatology: it is a useful agent in psoriasis vulgaris. Antitumor activity is another outstanding property of podophyllotoxines. It is effective in the treatment of Wilms tumors, different types of genital tumors (e.g., carcinoma verrucosus) and in non-Hodgkin and other lymphomas. Studies on penetration of podophyllotoxines into human bioengineered skin have demonstrated that the lignan induces acantholysis and cytolysis in the skin-equivalent model used for a wide variety of pharmacotoxicological trials. This might apply to claims of efficacy for cosmetic compounds. Three semisynthetic derivatives of podophyllotoxines etoposide, teniposide and etopophos are widely used as anticancer drugs and show good clinical effects against several types of neoplasms, including small cell lung cancers, lymphoma, leukemia, Kaposi’s sarcoma, etc.Etoposide is used in combination therapy in refractory testicular lymphoid and myceloid leukemia and in stomach, ovarian, brain, breast, pancreatic, and both small- and large-cell lung cancers. Teniposide is used less often than etoposide and it is mainly used to treat lymphomas. The successful derivatization of podophyllotoxines into etoposide and teniposide has generated interest in structure optimization to produce new derivatives with a superior pharmacological profile and broader therapeutic uses.

P. hexandrum has been reported to contain a number of bioactive molecules including flavonoids and lignans. Many flavonoids and lignans are already known for their antioxidant action and anti-apoptotic potential, and thus contribute towards radioprotection. Podophyllum hexandrum have anti-fungal activity, anti-inflammatory, insecticidal and anti-tumor activity.

2.4 Mechanism of action:

Medicinally in the removal of genital warts which was first used in 1942 with outstanding success. The Etoposide compound form is useful in anticancer drugs which kill the cancerous cells through the process of enzyme-mediated DNA scission. This blocks the action of the cell on the DNA of the cancer cells that will prevent their development, thereby killing them Etoposide is an anticancer agent, which belongs to the drug type topoisomerase inhibitor. Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme (which aids in DNA unwinding), prevents re-ligation of the DNA strands, and by doing so causes DNA strands to break. Etoposide is used as a form of chemotherapy for cancers such as Kaposi’s sarcoma, Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, nonlymphocytic leukemia, and glioblastoma multiforme. It is also sometimes used in aconditioning regimen prior to a bone marrow or blood stem cell transplant. Etoposide contraindicated in Hypersensitivity, pregnancy, lactation. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposideacts primarily in the G2 and S phases of the cycle. The mechanism of action appears to be related to the inhibition of type II topoisomerase activity since teniposide does not intercalate into DNA or bind strongly to DNA. Teniposide binds to and inhibits DNA topoisomerase II. The cytotoxic effects of teniposide are related to the relative number of double-stranded DNA breaks produced in cells, which are a reflection of the stabilization of a topoisomeraseII-DNA intermediate. Teniposide, when used with other chemotherapeutic agents for the treatment of all, results in severe myelosuppression. Teniposide used to treat childhood acute lymphocytic leukemia.

Table 6: Use of Phytoconstituents

Sr. No.	Analogues	Therapeutic use
1	Etoposide	Testicular cancer, Lung cancer, Kaposi’s sarcoma
2	Teniposide	Lymphoblastic leukemia

3. Taxus:

3.1 Description of Taxus bucket:

3.1.1 Taxonomical description:

Kingdom: Plantar

Order: Pinwales

Family: Taxanes

Genus: Taxus

Species: T. baccarat

Scientific name: Taxus baccarat

Common name: Common yew, European yew,

3.1.2 Geographical description:

This species is found in southwest Asia, western, central and southern Europe, Northwest Africa, and Northern Iran. This small to medium-sized evergreen slow growing tree is poisonous. Its lower elevation limit is 1 meters and upper elevation limit is 2500 meters.₎ Taxus baccarat is a conifer native to western, central and southern Europe, northwest Africa, northern Iran and southwest Asia. It is a native of temperate Himalayas, Afghanistan to Bhutan and Cassia Hills and upper Burma. It is the tree originally known as Yew, though with other related trees becoming known, it may now be known as English yew or European yew. It is also known as Himalayan yew.

3.1.3 Botanical description:

Taxus baccarat is an evergreen, under storey tree to 30m tall, with a spreading crown. It tends to be forked, fluted with depressions at branch stem junctions. Branches are ascending to drooping with twigs irregularly alternate, green or yellow green when young, reddish brown with age. The BARK is reddish grey or reddish brown, thin smooth, peeling off in longitudinal narrow shreds. LEAVES in to 2rows, needle like, 1.5-2.8 by 0.2-25cm, usually curved, acuminate. Margins, slightly in rolled, dark-green and shining above, brownish-yellow and somewhat pale beneath, single nerved and narrowing into a short petiole FLOWER Inconspicuous, yellowish with female blooms on small flaky handles. SEED hard, surrounded by a red fleshy aril, looking like a berry, about 7mm in diameter 5.

3.2 Phytoconstituents:

Leaves contain a volatile oil, tannic acid, Gallic acid and resinous substance called toxin. The prototype taxanes is the natural product paclitaxel, originally known as taxol. Docetaxol is semi- synthetic analogue of paclitaxel.

Table 8: Taxus Phytoconstituents

Sr. No.	Name
1	paclitaxel
2	Docetaxol

3.3 Use:

3.3.1 Ethno medicinal use:

Tridoshanut (mitigates all three doshas), Medha-shukrakar (promotes intelligence and semen), Ruchaya (helps taste), Rakshoghana (destroy evil spirits), Jwara-jantujita (curesfever, worms’ infestation), Hanti Kustha Asra Trit Daha Daurgandhaya Til-kalak (cures leprosy and other skindiseases, diseases of blood, thirst, burning sensation, bad smelland black spots (moles) of the skin. Balapushti-vivardhanam (strength promoting). Useful in Kasa, shwas, vata-shleshma vikar, gulma, agnimandaya, aruchi also.

3.3.2 Pharmacological use:

The Taxus baccarat tree is a highly toxic plant that has occasionally been used medicinally, mainly in the treatment of chest complaints. All parts of the plant, except the fleshy fruit, are antispasmodic, cardio tonic, diaphoretic, emmenagogue, expectorant, narcotic and purgative. Plant contain the substance "taxol" having anticancerous property. The leaves have been used internally in the treatment of asthma, bronchitis, hiccup, indigestion, rheumatism and epilepsy. Externally, the leaves have been used in a steam bath as a treatment for rheumatism. A homeopathic remedy is made from the young shoots and the berries. It is used in the treatment of many diseases including cystitis, eruptions, headaches, heart and kidney problems rheumatism etc. A tincture made from the young shoots of the plant, is used to cure headache with giddiness, feeble faltering pulse, coldness of the extremities, diarrhoea, general prostration and severebiliousness.

3.4 Mechanism of action:

Paclitaxel interferes with the normal function of microtubule growth. paclitaxel binds to the β subunit of tubulin. Tubulin isthe "building block" of microtubules, and the binding ofpaclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Further research has indicated that paclitaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.

Docetaxel:

This leads to a significant decrease in free tubulin needed for microtubule formation and results in inhibition of mitotic cell division between metaphase and anaphase, preventingfurther cancer cell progeny. Because microtubules do not disassemble in the presence of docetaxel, they accumulate inside the cell and cause initiation of apoptosis. Apoptosis isalso encouraged by the blocking of apoptosis-blocking Bcl-2oncoprotein. Both in vitro and in vivo analysis show the antineoplastic activity of docetaxel to be effective against a wide range of known cancer cells, cooperate with other antineoplastic agents’ activity, and have greater cytotoxicity thanpaclitaxel, possibly due to its more rapid intra cellular uptake.

Table 9: Use of Taxus Phytoconstituents

Sr. No.	Analogue	Therapeutic use
1	Paclitaxel	Ovarian cancer, Breast cancer, Kaposi’s sarcoma
2	Docetaxel	Prostate cancer, breast cancer, colorectal, Liver, Renal cancer

The main use of docetaxel is the treatment of a variety of cancers after the failure of anthracycline-based chemotherapy. Marketing of docetaxel as Taxol is mainly towards the treatment of breast, prostate and other non-small cell cancers. Clinical data has shown docetaxel to have cytotoxic activity against breast, colorectal, lung, ovarian, prostate, liver, renal, gastric, head and neck cancers, and melanoma.

4. Hemp:

4.1 Description of Cannabis sativa:

4.1.1 Taxonomical description:

Kingdom: Plantae

Order: Utricles

Family: Cannabaceae

Genus: Cannabis

Species: Cannabis Sativa

Common name: Cannabis sativa

Scientific name: Indian hemp ^[9]

4.1.2 Geographical description:

Cannabis sativa was originally a native of Western and Central Asia. It has been cultivated since ancient times in Asia and Europe. It spread to the New World in post Columbian times. Cannabis sativa has been cultivated for more than 4500 years for different purposes. Its medicinal value was discovered in India as Ayurvedic medicine and cultivated as early as 900 BC. In India cultivation of this plant is controlled and permitted only in the districts of Almora, Garhwal and Neonatal (Utterakhand, India) with small extent in Kashmir and Travancore.

4.1.3 Botanical description:

Indian hemp (Cannabis sativa L.) is an annual herb of the family Cannabinaceae having erected stems growing from 3to10 feet or more high, very slightly branched and having grayish-green hairs. The leaves are palmate, with five to seven leaflets, numerous, on long thin petioles with acute stipules at the base, linear-lanceolate, tapering at both ends and the margins sharply serrate. The flowers are unisexual, the male in axillary and terminal panicles, apetalous, with five yellowish petals and five parricidal stamens; the female flowers germinate in the axils and terminally, with one single-ovulate ovary. The fruit is small, smooth, light brownish-grey in color, and completely filled by the seed.

4.2 Phytoconstituents:

The chemical constituents of Cannabis represent almost all of the chemical classes, e.g., hydrocarbons, sugars, terrenes, steroids, flavonoids, nitrogenous compounds and amino acids. Out of these, the most specific class of Cannabis constituents is C terpenophenolic cannabinoid. In 1980the total number of natural compounds identified in Cannabis sativa was 423 in 1995 was 483 and in 2005 was 489. Out of 489 compounds, 70 were known as cannabinoid which is further classified into 11 categories (number known) such as Cannabigerol type, Cannabichromene type, Cannabidiol type, Δ⁹-trans-Tetrahydrocannabinol type, Δ⁸-trans-Tetrahydrocannabinol type.

Table 11: Hemp Phytoconstituents

Sr. No.	Name
1	Δ9-trans-Tetrahydrocannabinol
2	Δ8-trans-Tetrahydrocannabinol

4.3 Use:

4.3.1 Ethno medicinal use:

The plant parts which are consumed for various purposes are leaf, shoot and seed. It is used in the form of grain and in roasted mode. Seed may be used as raw or cooked. It can be dry and eaten as a condiment or made into cakes. Along with various methods of Cannabis consumption, smoking or oral consumption in much common. In general, it is considered that smoking produces more relaxing effect; in comparison to vaporizing and eating which tend to be more intense in effects. For oral consumption, Cannabis or its extract must be sufficiently heated or dehydrated to cause decarboxylation of its most abundant cannabinoid, tetra hydro cannabinoid acid, into psychoactive tetra hydro cannabinoid acid (Cannabisculture.com). Cannabis can also be consumed as a Cannabis tea. Cannabis was recommended for phlegm and diarrhea The modern Ayurvedic properties of Cannabises described by Chopra and Chopra (1957) are: paphahari (promoting loosening and elimination of phlegm), grahini (promoting retention and binding the bowels), pachani (promoting digestion), ushna (promoting heat), pitala (exciting the flow of bile), modavardhani (promoting happiness), vagvardhani (stimulating the digestive fire), dipani (stimulating appetite), ruchya (promoting taste), nidraprada (hypnotic)^[9]

4.3.2 Pharmacological use:

There are lots of literatures available on pharmacological activities and clinical trials of Cannabis sativa by using various model animals. In the following table one can find pharmacological studies of Cannabis on human these are: Allergenic effect, Analgesic effect, Anticancer activity, Antidepressant like activity, Antidiuretic activity, Antiemetic, Anti-inflammatory activity,Anti-tumor activity, Appetite enhancing, Bronchoconstrictor activity Cell death with shrinkage of Neurons, Central nervous system depressant activity, Digital necrosis, Gynecomastic effect, Hem agglutinin activity, Histamine release stimulant, Hyperglycemic activity, Immunomodulatory effect, Inflammatory effect, Mutagenic effect, Myocardial infarction, Pancreatic effect, Pancreatic toxicity, Psoriatic effect, Reproductive effect, Sexual headache, Spermicidal effect, Tumor-promoting effect.^[9]

4.4 Mechanism of action:

A significant amount of the research conducted so far on the mechanism of cannabinoid antitumor activity has focused on gloom cells. Initial studies showed that THC and other cannabinoid induce the apoptotic death of gloom cells by CB1- and CB2-dependent stimulation of the de novo synthesis of the pro-apoptotic sphingo lipid ceramide. Further studies based on the analysis of the gene expression profile of THC-sensitive and -resistant gloom cells yielded further insight into the specific signaling events downstream of ceramide that are activated in cancer cells by cannabinoid. Thus, it was found that treatment with THC results in enhanced expression of the stress-regulated protein p8 (NUPR1), a transcriptional regulator that has been implicated in the control of tumourigenesis and tumour progression, together with several of its downstream targets, such as the endoplasmic reticulum (ER) stress–related transcription factors ATF4 and CHOP, and the pseudokinase tribbles homologue 3 (TRIB3). This THC-triggered stimulation of the p8-regulated pathway enhances the inhibitory interaction of TRIB3 with a pro-survival kinase, AKT, which leads to inhibition of the mammalian target of rapamycin complex 1 (mTORC1) and the subsequent stimulation of autophagy-mediated cell death. ^[7]

Cannabinoid-induced apoptosis relies on the stimulation of endoplasmic reticular (ER) stress and autophagy. Here, the mechanism of cannabinoid-induced apoptosis in gloom, pancreatic, and hepatocellular carcinoma cells is depicted.

This signaling route could constitute the main mechanism of cannabinoid-induced cell death, with some variations inherent to different types of cancer cells.

CB1 = cannabinoid CB1 receptor; CB2 = cannabinoid CB2 receptor;

SPT = serine palmitoyltransferase;

elF2α = eukaryotic translation initiation factor 2α;

P inscribed in a circle = protein phosphorylation upon treatment with Δ⁹-tetrahydrocannabinol (THC);

ATF-4 = activating transcription factor 4;

CHOP = C/EBP homologous protein;

AKT = protein kinase B;

TRIB3 = tribbles-homologue 3;

mTORC2 = mammalian target of rapamycin complex 2;

CDKs = cyclin-dependent kinases;

pRb = retinoblastoma protein;

CaCMKKβ = calcium/calmodulin–dependent protein kinase kinase

2β; AMPK = AMP-activated protein kinase.

CONCLUSION:

From the present review, it can be concluded that cancer is the leading cause of death in developing countries like India. As there is an enormous increase in the population day by day, the alternative therapy in the market is getting its glimpse. The cheap herbal drug treatment may highly be recommended to the rural and poor people to treat effectively the cancers of various type is an ideal choice. In conclusion this article provides the knowledge about anticancer medicinal plants which are used by people all over the world the various Phytochemicals that may be used effectively for cancer treatment. The available literature finds to be very impressive which may give an indication for the therapeutic use fullness. Only few of the plants are listed here. The isolation, identification of active principles and pharmacological studies of the active Phytoconstituents may be considered and studied elaborately to treat effectively various types of cancer.

REFERENCE:

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9. O. P. Chaurasia, B. Ballabh, A. Tayade, Raj Kumar, G. Phani Kumar And S. B. Singh, Podophyllum L: An Endergered and Anticancerous Medicinal Plant- An Overview, Indian Journal of Traditional Knowledge, 2012

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18. Thaneshwar Subedi, Phytochemical Studies of Taxus Species and Their Uses in Cancer Treatment: Review Article, Janapriya Journal of Interdisciplinary Studies Vol. 6, 2017.

19. Wesam Kooti, Karo Servatyari, Masoud Behzadifar, Majid Asadi Samani, Fatemeh Sedeghi, Bijan Nouri, Hadi Zare Marzouri, Effective Medicinal Plant in Cancer Treatment, Part 2: Review Study, Journal of Evidence Based Integrative Medicine, 2017.

Received on 31.08.2020 Modified on 17.09.2020

Res. J. Pharmacognosy and Phytochem. 2020; 12(4):235-244.

DOI: 10.5958/0975-4385.2020.00040.0

Sr No.	Brand Name	Manufacturer	Content in Formulation	Route of Administration	Use	Adverse Effect
1	Uniblastine	United Biotech Pvt Ltd	10 mg	Intrathecal /intravenous	Breast Cancer, Hodgkin’s disease	Nausea, Vomiting Decreased appetite
2	Cytoblastine	Cipla Ltd	10 mg	Intravenous	Breast Cancer, Hodgkin’s disease	Nauseam Vomiting Decreased Appetite
3	Cytocristine	Cipla Ltd	1 ml	Intravenous	Lung cancer, Pancreatic cancer	Hair loss, constipation