Plants Used In Cancer Treatment

Plants Used In Cancer Treatment Part - I Cancer     What is cancer? US cancer statistics Cancer costs Most frequent cancers by organ effected 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  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 Lilly Pharmaceuticals      Svoboda injected a crude extract of the whole periwinkle plant into mice that were infected with P-1534 leukemia 60-80% of the mice experienced prolonged life Lilly produced vinblastin as the drug Velban Also synthesized another alkaloid, vincristine (VCR), as the drug Oncovin First human tests in 1960 - 49 yr old man dying of Hodgkin’s disease - within one week man was walking - 4 months later the tumor gone More alkaloids in periwinkle Overall 70 alkaloids have been identified in periwinkle  Some have anticancer properties  Some lower blood sugar levels  Some act as hemostatics (arrest bleeding)  Periwinkles also contain the alkaloids reserpine and serpentine, which are powerful tranquilizer  Vincristine and vinblastine      Major chemotherapeutic agents 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 Gave researchers hope that some cancers can be overcome by simple chemotherapy Today used for other types of cancers 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 Potent Drugs They are all administered intravenously once a week  Cmpds are fatal if they're administered any other way, and can cause a lot of tissue irritation if they leak out of the vein.  Compounds are very similar in structure and have the same basic action, they have distinctly different effects on the body.  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  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