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									Plants Used In Cancer Treatment

            Part - I
   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
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
       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
   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 dose-
  limiting factor
 Caused severe birth defects in lab animals
  so not used on pregnant patients
   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
   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
   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
   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,

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