Plants Used In Cancer Treatment

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Plants Used In Cancer Treatment

• Part - I

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Cancer

• What is cancer?
• US cancer statistics
• Cancer costs
• Most frequent cancers by organ effected

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Major types of cancers

• Over 200 types of cancer are known grouped into
  major categories
• Carcinomas
• Sarcomas
• Melanomas
• Teratomas
• Leukemias and Lymphomas

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History of Cancer Therapy

• Folk remedies
• NCI 1955
• NCI-USDA late 1950s
• NCI 1985
• 21st century

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Current Plant Based Therapies

• Periwinkle
• Mayapple
• Yew
• Camptotheca
• Lapachol

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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

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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

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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

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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 Hodgkins disease - within one week man was
  walking - 4 months later the tumor gone

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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

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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

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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

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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.

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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

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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

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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)

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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

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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

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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