Tumour inhibitors from plants final
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  • 1. Siddhesh S. Bhende Ad. No. : 2009-12-120 Dept.: Plantation crops and Spices
  • 2. 4-Ipomeanol O O OH Lapachol O OH O Bruceantin O COCH3HO O O O O OH O HO H HH H N N O O O OH Camptothecin
  • 3. TUMOUR A mass of excess tissue that results from abnormal cell division. Tumors perform no useful body function. They may be benign (not cancerous) or malignant (cancerous) . CANCER A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues a nd can spread through the bloodstream and lymphatic sy stem to other parts of the body.
  • 4.  Cancer is a dreadful disease and is the second major cause of deaths after cardiovascular diseases  It is a growing public problem whose estimated worldwide new incidence is about 6 million cases per year  The incidence of various forms of cancer is now rapidly rising world wide  so combating this disease is of paramount importance to public health
  • 5. Forms of cancer treatments are Surgery Chemotherapy Immunotherapy Radiation
  • 6. Impact of chemotherapeutical agents…  They are highly reactive and non- selective  They cause serious unpleasant side effects like Nausea , Vomiting , fatigue , anemia , taste and smell changes , infection , infertility etc
  • 7. A successful anti cancerous drug should…….  Kill cancer cells without causing damage to normal cells  Plant based therapeutic agents will help to overcome this problem to some extent
  • 8. Plant derived anticancer agents inPlant derived anticancer agents in clinical useclinical use
  • 9. Vincristine & Vinblastine  First clinically used theraputic drug  Obtained from: Catharanthus roseus  Family : Apocyanaceae  Used for treating a variety of cancers including leukaemia, lymphomas, advanced testicular cancer, breast and lung cancer  Vincristine effective for treating acute childhood leukemia  Vinblastine has been especially effective for treating Hodgkin's disease 1
  • 10. One of the most promising plant- derived anticancer agents to be identified in recent years is the taxane- diterpenoid taxol (paclitaxel) Clinically introduced into US market in 1990s: isolated from the bark of Pacific yew tree,Taxus brevifolia (Taxaceae). : very low yield (0.01-0.03%) –the bark from 3 trees is needed to produce 1 gram of taxol! Paclitaxel ( Taxol ) Taxus brevifolia 2  Obtained from : Taxus brevifolia  Bark  Active against advanced breast cancer, ovarian cancer and lung cancer
  • 11. 3 Camptothecin  Isolated from : Camptotheca acuminata  Its synthetic derivatives are topotecan and irinotecan  Irinotecan: used for treating colo rectal cancer  Topotecan– used for the treatment of ovarian and small cell lung cancer
  • 12. Podophyllotoxin≈epiphyllotoxin4  Isolated from rhizomes of : Podophyllum peltatum : Podophyllum emodi Its semi synthetic derivatives are used in the cancer treatment .  Etoposide :cancer, lymphomas and leukaemias  Teniposide: paediatric cancer,neuroblastoma brain tumours
  • 13. Harringtonine and Homoharringtonine….  Alkaloid obtained from: Cephalotaxus harringtonia var.drupacea  Used in China : acute leukaemia  Officinal part: seeds 5
  • 14. Ellipticine and 9-methoxy ellipticine  Obtained from : Ochrosia elliptica  Treatment of breast cancer  They also inhibit broad spectrum preclinical side-effects like haemolysis, cardiovascular effect  Marketed in France 6
  • 15. Combrestatin A-4 (cis-stilbene)  Combrestatin A-4 (cis-stilbene)  African bush willow tree Combretum caffrum (Combretaceae). 7
  • 16. Folk medicines as potential anticancer drugs An alternative solution to allopathic medicine embodied with severe side effects, is the use of folk medicine plant preparations to arrest the insidious nature of the disease .
  • 17.  Apocynin  Isolated from Picrorrhiza kurroa (katuka) roots & rhizome  NADPH oxidase inhibitor  Has anti-oxidant and anti-inflammatory activity (Basu, 1971). Picrorrhiza kurroaPicrorrhiza kurroa
  • 18.  Plumbagin  From Plumbago zeylanica roots  Has anti cancer activity  Plumbagin inhibit exponentially growing tumours Plumbago rosea & P.zeylanicaPlumbago rosea & P.zeylanica
  • 19. Glycyrrhiza glabraGlycyrrhiza glabra  Glycyrrhizin  Obtained from rhizome  It will inhibit DNA and RNA synthesis (Badam L. 1994).
  • 20. Butea monospermaButea monosperma  Famous tree known as - the flame of forest  Flavone glycoside from leaves  Inhibited tumour cells in experimental models (Tirupathi, 2007).
  • 21. Withania somnifera  Withanolides  Present in the whole plant.  They are believed to be immuno modulators having anticancer activity (Ali M, Shuaib M 1997).
  • 22. New natural products with antitumour activity *The systematic screening programmes have resulted in the isolation of many new natural products exhibiting antitumour activity. A number of them have been considered sufficiently active for clinical studies.
  • 23. Tylocrebine Alkaloid from Tylophora crebiflora (Apocynaceae) in clinical trial unmanageable CNS effects
  • 24. *Thalicarpine (Thalictrum dasycarpum, Ranunculaceae) *Tetrandrine (Cyclea peltata, Menispermaceae) alkaloids clinical trials showed no anti tumour activity Thalictrum dasycarpum However tetrandrine was found to be able to block calcium channel hence useful in the treatment of CVD
  • 25. Quassinoids or Simaroubolides Alkaloides isolated from a variety of plants in the Simaroubaceae family are currently of interest for their for antitumour properties. Bruceantin *alkaloid from Brucea antidysenterica * used to treat cancer in Ethiopia *shows high anti leukaemic activity at low dose *acts through inhibition of protein synthesis
  • 26. Maytansinoids From Maytenus serrata and other species of Maytenus, mosses and Actinomycete Maytenus ilicifolia (Celastraceae) *Active against several neoplasms at *Mitotic inhibitor
  • 27. •From Tripterygium wilfordii (Celastraceae) •potent anti leukaemic agents contains only small amounts • In China crude extract of this plant is used in inflammatory and immune disorders Triptolide andTripdiolide
  • 28. Phyllanthostatin and phyllanthoside  A complex mixt. with marked antitumour properties  Obtained from the root of central American tree, Phyllanthus cuminatus
  • 29. Mechanism of action of antiMechanism of action of anti cancerous drug…..cancerous drug…..  Mechanism of action differ widely among various chemotherapy agents  Because they have different chemical structure  majority of cancer chemotherapy drugs act by inhibiting the nucleic acid synthesis  there is no common feature to explain their biological activity  They can act as Mitotic poison, DNA inhibitors or Alkylating agents
  • 30. Mitotic poisonsMitotic poisons Colchicum speciosum Gloriosa superba  Colchicine, Podophyllotoxine &Vincristine  They act by binding to tubulin (protein in mitotic spindle)  During mitosis, the chromosome separate with the assistance of these microtubules
  • 31. DNA Inhibitors  Camptothecin  Inhibit DNA synthesis and replication through enzyme topoisomerase I.
  • 32. Alkylating agent  A large number of natural tumor inhibitor acts as alkylating agent become they posses highly electrophilic centers and their action is through alkylation of nucleophilic group in the enzyme that control cell division.  Eg; Cucurbitacin, Bruceantin, Triptolide, Elephantopin  Most of these compounds are cytotoxic killing both normal and cancer cell.
  • 33.  Antioxidants  Free radical scavengers  Inhibitors of (lipoxygenase & urokinase ) enzymes involved in cell division Action of Phytochemicals isolated fromAction of Phytochemicals isolated from folk medicines…..folk medicines…..
  • 34. Curcuma  Curcumin, a natural component of the rhizome of curcuma has emerged as one of the most powerful chemopreventive and anticancer agents.  Its biological effects are antioxidant and anti-inflammatory
  • 35.  Artemisinin, is a natural product from antimalarial Chinese herb Artemisia annua L.  Artemisinin and its derivatives are active against cancer cells. (Li. et al, 2008). Artemisia
  • 36.  Annona glabra (pond apple), a tropical tree growing wild in the Americas and Asia.  Used in traditional medicine against several human ailments, including cancer. (Cochrane et al, 2008). Pond Apple
  • 37. The seed of Strychnos nux-vomica (Loganiaceae) has been used in traditional Oriental medicine as a folk remedy for the treatment of cancer. water extract of Strychnin seeds affect the growth of human gastric carcinoma cells. (Lee et al, 2008). Nux-vomica
  • 38. Dandelions  Taraxacum, commonly known as dandelions, have a history of use in Chinese, Arabian and Native American traditional medicine, to treat cancer.  Crude extract of dandelion leaf (DLE) decreased the growth of breast cancer cells
  • 39.  Brucea javanica fruit is reported to have anticancer properties in Chinese medicine and its extract has been shown to possess anti proliferative on human carcinoma cells.  These findings are significant in the development of traditional Chinese medicine as an alternative treatment for pancreatic cancer (Lau et al, 2008). Brucea
  • 40. Some food materials with anti cancerous property …….
  • 41. Green TeaGreen Tea  Numerous in vivo and in vitro studies indicate strong chemopreventive effects for green tea and its constituents against cancers of various organs.  (-)-Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, appears to be the most biologically active constituent in tea with respect to inhibiting cell proliferation
  • 42.  Ginger is a common condiment for various foods and beverages.  Some pungent constituents (gingerol, zingerone and paradol ) present in ginger exhibit cancer preventive activity. Ginger
  • 43. Fenugreek  A naturally occurring edible spice as an anticancer agent.  The extract from the seeds of fenugreek, is cytotoxic in vitro to a panel of cancer but not normal cells.
  • 44. Flaxseed oil  Flax lignans belonging to the phytoestrogens are metabolised after ingestion into enterolignans that may offer a protection against the onset and development of hormono-dependant cancers.
  • 45. Flaxseed oil  Flax lignans belonging to the phytoestrogens are metabolised after ingestion into enterolignans that may offer a protection against the onset and development of hormono-dependant cancers.
  • 46. sesame seed  The mammalian lignans, which are produced by the microflora in the colon of humans and animals from precursors in foods, have been suggested to have potential anticancer effects  Sesame seed, alone and in combination with flaxseed, produces mammalian lignans equivalent to those obtained from flaxseed alone.
  • 47. Soybean  The soy isoflavones have antiproliferative effects on a variety of cancer types.  Lunasin of soy is a novel seed peptide for cancer prevention.  Recent studies have demonstrated a direct effect of soy saponins on cancer cells
  • 48. Tomato high consumption of tomatoes effectively lowers the risk of reactive oxygen species (ROS)-mediated diseases such as cardiovascular disease and cancer by improving the antioxidant capacity.
  • 49. Strawberry Compounds in strawberries have demonstrated anticancer activity in several different experimental systems, blocking initiation of carcinogenesis, and suppressing progression and proliferation of tumors.
  • 50. Citrus fruits  flavonoids (hesperidin) have a protective effect against cardiovascular diseases and some types of cancer.  Limonoids are a prominent group of secondary metabolites in citrus fruit with anticancer effect
  • 51. Cruciferous vegetables  Indole-3-carbinol (I3C), a naturally occurring compound found in vegetables of the Brassica genus, such as broccoli and cabbage, is a promising anticancer agent  Cruciferous vegetables decreased the risk of breast cancer by 40 percent.
  • 52. Crude extract Solvent extraction (inactive materials removed) Structure of active cpd. is elucidatied MS, NMR, IR, UV and X-ray crystallography Treatment with weak acids/bases Column chromatography TLC, HPLC Pure active ingredient Isolation and purification of active ingredient
  • 53. Purified natural product tested against a range of standard experimental neoplasms preclinical toxicological studies (large amounts of material will be required) clinical studies high therapeutic index and low side effects
  • 54. Number of screens Preliminary screening test 25,000 (per year) Preclinical testing 8-12 Clinical trials 6-8 Slightly less than half of these may be plant-derived.
  • 55. Availability of natural source  Availability of the plant source has to be ensured  If common, collected from wild, but commercial cultivation is better  Search for alternate source – related species  Synthesis of active chemical through tissue culture – best option
  • 56. Conclusion  Though the antitumour screening programmes have resulted in the identification of a number of antitumour agents, only small number of drugs have been developed  Majority of these drugs are effective against rapidly proliferating tumours  However, slow growing tumours still respond poorly to chemotherapy  Rapidly dividing natural tissues suffer toxic effect from the administered drug , leading to the major side effect in cancer chemotherapy like bone marrow repression, nausea, vomiting etc
  • 57. • All these facts points out to the need for the development of drugs that will separately and specifically affect the human cancer tissues without damaging any normal tissue  Ayurvedic therapy was found to be able to cure chronic diseases better, which were previously not amenable to treatment by western medical practices.  Its systematic study and understanding is also worth considering by pharmaceutical industries in order to develop their active ingredients as allopathic drugs for cancer treatment.