1. Plants Used In Cancer Treatment Part - I

2. Cancer n What is cancer? n US cancer statistics n Cancer costs n Most frequent cancers by organ effected

3. Cost of cancer per year in U.S.

6. Major types of cancers n Over 200 types of cancer are known grouped into major categories  Carcinomas  Sarcomas  Melanomas  Teratomas  Leukemias and Lymphomas

7. History of Cancer Therapy n Folk remedies n NCI – 1955 n NCI-USDA – late 1950s n NCI – 1985 n 21 st century

8. Current Plant Based Therapies n Periwinkle n Mayapple n Yew n Camptotheca n Lapachol n Others: Aspergillus fumigatus, Viscum album

9. Madagascar Periwinkle – Vinca alkaloids n Catharanthus roseus is known as the common or Madagascar periwinkle, n Formerly classified as Vinca rosea n Perennial evergreen herb in Apocynaceae n Originally native to island of Madagascar

11. Traditional uses of periwinkle n Used to treat a wide assortment of diseases  In Europe, folk remedy for diabetes for centuries  In India, juice from the leaves to treat wasp stings.  In Hawaii, boiled to make a poultice to stop bleeding.  In China, an astringent, diuretic and cough remedy.  In Central and South America, homemade cold remedy to ease lung congestion and inflammation and sore throats  Throughout the Caribbean, an flower extract to treat eye irritation and infections

12. Interest in Periwinkle n Two groups began independently working on periwinkle in 1950s when they learned of a tea Jamaicans were drinking to treat diabetes  Univ of Western Ontario - Beer and Noble -interested in plant as a possible “oral insulin” - they isolated alkalod - vinblastin  Eli Lilly Pharmaceuticals - Svoboda

13. More alkaloids in periwinkle n Overall 70 alkaloids have been identified in periwinkle with various uses – anticancer properties – lower blood sugar levels – hemostatics (arrest bleeding) – reserpine and serpentine - tranquilizers

14. Vincristine and vinblastine n Vincristine has been especially effective for treating acute childhood leukemia, often with 99% remission rates n Vinblastine has been especially effective for treating Hodgkin's disease - which had been considered a fatal up to that point

15. Mode of action of vinca alkaloids n Vinblastine, vincristine, and two semi-synthetic derivatives (vindesine and vinorelbine) all have the same mode of action n Inhibit mitosis in metaphase by binding tubulin

19. Vinblastine n Marketed as Velban n Half-life in the bloodstream of 24 hours n Vinblastine is mainly useful for treating Hodgkin's disease, lymphocytic lymphoma, histiocytic lymphoma, advanced testicular cancer, advanced breast cancer, Kaposi's sarcoma n Another action: It also seems to fight cancer by interfering with glutamic acid metabolism

20. Side effects of vinblastine n Side effects include hair loss, nausea, lowered blood cell counts, headache, stomach pain, numbness, constipation and mouth sores n Bone marrow damage is the typical dose- limiting factor n Caused severe birth defects in lab animals so not used on pregnant patients

21. Vincristine n Marketed as Oncovin n Serum half-life of about 85 hours. n Used mainly to treat acute leukemia, rhabdomyosarcoma, neuroblastoma, Hodgkin's disease and other lymphomas n Also Wilms' tumor (80%) and Burkitt's lymphoma (50%), when used in combination with other drugs n Neurotoxicity is the dose limiting factor (it can cause damage to the peripheral nervous system)

22. Side effects of vincristine n Same as those found with vinblastine n Nervous system problems such as sensory impairment n Breathing problems or lung spasms shortly after the drug is administered n Secondary cancers if they receive the drug along with other anticancer drugs that are known to be carcinogens n Severe birth defects in animal tests

23. Vindesine -semi synthetic n Marketed as Eldisine and Fildesin n Serum half-life of about 24 hours n Mainly to treat melanoma and lung cancers (carcinomas) and, with other drugs, to treat uterine cancers n Toxicity and side effects are similar to those of vinblastine

24. Vinorelbine - semi-synthetic n Marketed as Navelbine n Approved for non-small cell lung cancer and breast cancer – usually in combination with other drugs n Clinical trials on-going as a treatment for ovarian, cervical, prostrate and other cancers n Seems to have a wider range of antitumor activity than the other vinca alkaloids n Side effects include diarrhea, nausea, hair loss, leukopenia