Plants Used In Cancer Treatment Part - I. Cancer n What is cancer? n US cancer statistics n Cancer costs n Most frequent cancers by organ effected.

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 dose-limiting 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