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Plants Used In Cancer Treatment Part - I Cancer What is cancer? US cancer statistics Cancer costs Most frequent cancers by organ effected Cost of cancer per year in U.S. Major types of cancers Over 200 types of cancer are known grouped into major categories Carcinomas Sarcomas Melanomas Teratomas Leukemias and Lymphomas History of Cancer Therapy Folk remedies NCI – 1955 NCI-USDA – late 1950s NCI – 1985 21st century Current Plant Based Therapies Periwinkle Mayapple Yew Camptotheca Lapachol Others: Aspergillus fumigatus, Viscum album Madagascar Periwinkle – Vinca alkaloids Catharanthus roseus is known as the common or Madagascar periwinkle, Formerly classified as Vinca rosea Perennial evergreen herb in Apocynaceae Originally native to island of Madagascar Traditional uses of periwinkle 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 Interest in Periwinkle 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 More alkaloids in periwinkle Overall 70 alkaloids have been identified in periwinkle with various uses – – – – anticancer properties lower blood sugar levels hemostatics (arrest bleeding) reserpine and serpentine - tranquilizers Vincristine and vinblastine Vincristine has been especially effective for treating acute childhood leukemia, often with 99% remission rates Vinblastine has been especially effective for treating Hodgkin's disease - which had been considered a fatal up to that point Mode of action of vinca alkaloids Vinblastine, vincristine, and two semi-synthetic derivatives (vindesine and vinorelbine) all have the same mode of action Inhibit mitosis in metaphase by binding tubulin Vinblastine Marketed as Velban Half-life in the bloodstream of 24 hours Vinblastine is mainly useful for treating Hodgkin's disease, lymphocytic lymphoma, histiocytic lymphoma, advanced testicular cancer, advanced breast cancer, Kaposi's sarcoma Another action: It also seems to fight cancer by interfering with glutamic acid metabolism Side effects of vinblastine Side effects include hair loss, nausea, lowered blood cell counts, headache, stomach pain, numbness, constipation and mouth sores Bone marrow damage is the typical doselimiting factor Caused severe birth defects in lab animals so not used on pregnant patients Vincristine Marketed as Oncovin Serum half-life of about 85 hours. Used mainly to treat acute leukemia, rhabdomyosarcoma, neuroblastoma, Hodgkin's disease and other lymphomas Also Wilms' tumor (80%) and Burkitt's lymphoma (50%), when used in combination with other drugs Neurotoxicity is the dose limiting factor (it can cause damage to the peripheral nervous system) Side effects of vincristine Same as those found with vinblastine Nervous system problems such as sensory impairment Breathing problems or lung spasms shortly after the drug is administered Secondary cancers if they receive the drug along with other anticancer drugs that are known to be carcinogens Severe birth defects in animal tests Vindesine -semi synthetic Marketed as Eldisine and Fildesin Serum half-life of about 24 hours Mainly to treat melanoma and lung cancers (carcinomas) and, with other drugs, to treat uterine cancers Toxicity and side effects are similar to those of vinblastine Vinorelbine - semi-synthetic Marketed as Navelbine Approved for non-small cell lung cancer and breast cancer – usually in combination with other drugs Clinical trials on-going as a treatment for ovarian, cervical, prostrate and other cancers Seems to have a wider range of antitumor activity than the other vinca alkaloids Side effects include diarrhea, nausea, hair loss, leukopenia