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Plants Used In Cancer Treatment

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Title: Plants Used In Cancer Treatment


1
Plants Used In Cancer Treatment
  • Part - I

2
Cancer
  • Cancer is a diverse group of diseases
    characterized by uncontrolled growth of abnormal
    cells
  • Cells divide more frequently than normal cells
    and do so in a disorderly fashion, producing
    tumors and other imbalances in cell numbers .
  • Forms of cancer attack all parts of the body and
    victims of all ages
  • In US alone over half a million people die from
    cancer each year - 2nd leading cause of death
  • Cancer costs billions of dollars in medical
    expenses just in the United States

3
Major locations of cancer
  • Cancers of the prostate, breast, lung, and colon
    account for 56 of all cases in the U.S.
  • These are the leading causes of cancer deaths for
    all racial and ethnic groups
  • Lung cancer accounts for only 13 of all cases
    but causes 29 of all cancer deaths, making it
    the leading cause of cancer deaths

4
Major types of cancers
  • Over 200 types of cancer are known grouped into
    major categories
  • Carcinomas
  • Sarcomas
  • Melanomas
  • Teratomas
  • Leukemias and Lymphomas

5
Carcinomas
  • Develop from epithelial cells, such as the inside
    of the cheek or the lining of the intestine
  • Can occur in many regions of body - glands,
    ducts, mucus membranes
  • esophagus, stomach, colon, intestines

6
Sarcomas
  • Develop in connective and supporting tissues
    (e.g., muscle, cartilage, bone, fatty tissues)
  • Often very malignant increasing rapidly in size
    and invading neighboring tissues

7
Melanomas
  • Type of skin cancer often occurring on legs,
    neck, and head
  • Often spreads rapidly
  • Frequently seen as a black mole (containing
    melanin)

8
Other Types
  • Teratomas arise from embryonic cells that may be
    present in ovary, testicles, and other areas
  • Leukemias and lymphomas cancer of blood and lymph
    forming tissues (i.e. bone marrow, spleen,
    thymus) which involve cell divisions in body
    fluids characterized by excess of white blood
    cells

9
Cancer Therapy
  • Search for cancer cures is relentless
  • Plants have figured prominently in folk remedies
    for cancer
  • Over 3000 plant species had been used
  • Ancient records from Egypt (Ebers Papyrus), from
    India, from Greece, and Rome all contain
    direction for plant use to treat various cancers

10
Modern Search for drugs
  • Beginning in 1955 National Cancer Institute (one
    of the NIH institute) began intensive screening
    process to find anti-cancer compounds
  • Initially screening was just on synthetic
    chemicals - over 400,000 compounds tested
  • Expanded to microbial products and then plant
    extracts - initially very few plants

11
Search expands to plants
  • In the late 1950's National Cancer Institute and
    USDA began major search for plants with
    anti-cancer properties
  • Thousands of plants were scientifically screened,
    and several have become standard chemotherapy for
    different forms of cancers
  • In early 1980s program was discontinued because
    few new compounds developed
  • Problem may have been screening assay because
    only using mouse leukemia cell line

12
New screening renewed interest in plants and
other natural products
  • Starting in 1985 new screening assays were
    developed by NCI using diverse panel of human
    tumor cell lines
  • 60 human cell lines from nine cancer types
    (leukemia, lung, colon, CNS, melanoma, ovarian,
    renal, prostate, and breast)
  • Preliminary screening with 3 cell lines and
    positive extracts tested on all 60

13
Search continues today
  • Search is not over since only a small percentage
    of plants have been screened
  • Major push on plants from tropical and
    subtropical regions of world through major
    research institutes
  • Missouri Botanical Garden
  • New York Botanical Gardem
  • University of Chicago
  • Also big push on fungi, cyanobacteria, and marine
    organisms
  • Especially interested in treatments for solid
    tumors

14
Current Plant Based Therapies
  • Periwinkle
  • Mayapple
  • Yew
  • Camptotheca
  • Lapachol

15
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
  • Widely cultivated for hundreds of years and now
    found growing wild in most warm regions of world,
    including the Southern US

16
Madagascar Periwinkle
  • The plants grow one or two feet high,
  • Glossy, dark green leaves (1-2 in. long)
  • Flowers all summer
  • Flower colors from white to pink to purple

17
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18
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

19
Interest in Periwinkle
  • Researchers noticed the plant in the 1950's when
    they learned of a tea Jamaicans were drinking to
    treat diabetes
  • Two groups began independently working on
    periwinkle
  • Univ of Western Ontario - Beer and Noble
    -interested in plant as a possible oral insulin
    - they isolated alkalod - vinblastin
  • Eli Lilly Pharmaceuticals - Svoboda -

20
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 mos tumor gone

21
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

22
Use today
  • 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

23
More success
  • Vincristine is also a major cure of Wilms' tumor
    (80) and Burkitt's lymphoma (50), when used in
    combination with other drugs
  • Both alkaloids also used for other types of
    cancers
  • Periwinkle gave researchers hope that some types
    of cancers can be overcome by simple chemotherapy

24
Mode of action of vinca alkaloids
  • Vinblastine, vincristine, and two sem-synthetic
    derivatives (vindesine and vinorelbine) all have
    the same mode of action
  • Inhibit mitosis in metaphase
  • Bind to tubulin monomers, thus preventing the
    cell from making the spindles it needs to
    separate the chromosomes
  • Some evidence that they also inhibit cells
    ability to synthesize both DNA and RNA

25
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28
Potent Drugs
  • They are all administered intravenously once a
    week these solutions are
  • All 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.

29
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

30
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
  • Cause severe birth defects in lab animals so not
    used on pregnant patients

31
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.
  • Neurotoxicity is the dose limiting factor (it can
    cause damage to the peripheral nervous system)

32
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

33
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

34
Vinorelbine - semi-synthetic
  • Still in clinical trials - will be marketed as
    navelbine if approved
  • Clinical trials as a treatment for ovarian cancer
  • Seems to have a wider range of antitumor activity
    than the other vinca alkaloids
  • In preclinical trials, it showed promise in
    treating epithelial ovarian cancers and, in
    combination with other drugs, non-small-cell lung
    cancers
  • Side effects include diarrhea, nausea, hair loss,
    leukopenia
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