Madagascar periwinkle (Catharanthus roseus)
APOCYNACEAE, Dogbane Family
Centuries ago human populations were devastated by infectious diseases, but now death in western societies is biologically caused mostly by cardiopulmonary diseases and cancer. In North America alone over half a million people die from cancer each year. Fears of cancer are justified, because when left unchecked, many types ultimately or in short order are fatal to the host, and even if treated, many types of cancer are terminal diseases. Forms of cancer attack all parts of the body and victims of all ages, embattling lives of families and friends along with the victims, and costing billions of dollars in medical expenses just in the United States.
Cancers--over 200 known types--are caused by the rapid and uncontrolled formation of abnormal cells. The human body has more than 10,000,000,000 cells, many of which regularly undergo cell division. During cancer, cells of a particular tissue somehow are affected to divide more frequently than normal cells and do so in a disorderly fashion, producing tumors and other imbalances in cell numbers. Four major types of cancers are recognized: (1) carcinomas, which originate as a sheet of cells on a surface (e.g., skin, nose, lung, breast, prostate); (2) sarcomas, which develop in supporting tissues (e.g., muscle and bone); (3) teratomas, which arise from embryonic cells; and (4) leukemias and lymphomas, which involve cell divisions in body fluids. Two instances of noncancerous abnormal growths are warts and psoriasis (and the heartbreak thereof).
Civilization has known about cancer for thousands of years, and ancient mummies attest to the presence of cancerous tumors on all continents in prehistoric times. No culture claimed to have had a total cure for cancer, but some plants were used to treat cancer victims. Knowing this, in 1955 the United States government established the Cancer Chemotherapy National Service Center (CCNSC), whose job it was to screen natural and synthetic substances for anticancer activity. This center utilized a rapid (48 hr) test invented in 1942 by Dr. Alfred Taylor. Fertile chicken eggs were infected with cancer cells, and a compound to be tested was injected into the infected yolk sac to observe what effects the substance had on cancer and chick embryo growth. Many thousands of compounds were thus tested, including plants from around the world, and hundreds of plants are now known to have some inhibitory effect on cancer growth.
One plant, somewhat unknown earlier, changed the course of anticancer research. Madagascar periwinkle, Catharanthus roseus (formerly Vinca rosea), is a common house or garden plant in many regions, and this plant was used in folk medicine for treating dysentery, menstrual disorders, toothaches, and especially diabetes. In the mid-1950s interest was drawn to this species. Two programs were started, by Doctors C.T. Beer and R.L. Noble at the University of Western Ontario and by Dr. Gordon Svoboda of Lilly Corporation, a large drug-manufacturing company. Beer and Nobel were investigating this periwinkle as a possible oral insulin substitute, and in the laboratory Beer crystallized from leaves an alkaloid called vincaleukoblastine (VLB). Working independently at Lilly, Svoboda, in December 1957, injected a crude extract of the whole periwinkle plant into mice that were infected with P-1534 leukemia. To his amazement, 60-80% of the mice experienced prolonged life. Lilly produced VLB as the drug Velban and synthesized another alkaloid, vincristine (VCR), as the drug Oncovin.
VLB was finally tested on a human subject on 2 March, 1960. Velban was given to a 49-year-old man who was dying of Hodgkin's disease and had a huge tumor pressing against his windpipe. In four days the patient was comfortable; in one week he was walking again; and in four months the tumor was gone and the patient returned to work in a healthy condition. His condition remained stable for two and a half year with biweekly doses of Velban, until symptoms returned because the disease had grown resistant to the drug. Then Oncovin was given, which suppressed the disease.
Stories like these miracle cures with Madagascar periwinkle are now commonplace in medicine. Velban and Oncovin are regularly used in treatment of Hodgkin's disease, which was once considered hopelessly fatal, and the drugs being used produced initially over 40% survival after five years of treatment. Perhaps more impressive was use of VCR as the main treatment of acute lymphocytic leukemia in children, with a whopping 99% remission and 50% survival rate after three years. VCR is also a major cure of Wilms' tumor (80%) and Burkitt's lymphoma (50%), when used in combination with other drugs. [Cure here means no detection of cancer cells after five years of testing.] Madagascar periwinkle single-handedly gave researchers hope that some types of cancers can be overcome by simple chemotherapy, thus avoiding costly and deleterious radiation treatments for children and adults.
Hodgkin's disease is still very tough to fight, because it frequently involves lymph nodes, especially in cervical regions. Actually malignant cells form only a minority of the tumor, which characteristically had giant cells. Pusey (1902) first used radiotherapy to treat Hodgkin's disease, and his methods were refined in the 1940s and 1950s. Then was added single-agent chemotherapy with a form of mustard gas. The first effective combination chemotherapy was mustard gas with VLB, which in the 1960s had the above cure rates. Hodgkin's disease attacks 2.5 males per 100,000 and 1.5 females per 100,000 in the United States. Highest incidence is bimodal: 20-34 years and over 60. Using single-agent therapy VLB (now called vinblastine) has had a 68% response and 30% complete remission; VCR has had a 58% response and 36% complete remission. Used in a chemoseries either is more effective. Nitrogen mustard or cyclophosphamide are still used, but results are particularly high with procarbazine (107 of 159 had no relapse in one study) and Prednisolone or Prednisone.
Other plants produce natural substances that have some demonstrated anticancer effects. The may apple (Podophyllum peltatum), a common herbaceous plant of the north temperate region, was used by the Penobscot Indians of Maine to treat cancer, and research has shown that the alkaloid podophyllin and its derivatives slow growth of certain tumors, such as in venereal warts (condyloma acuminata). Bloodroot (Sanguinaria canadensis), another northern herbaceous plant that has red sap (latex), was widely used by American Indians and in European folk medicines. One recipe from the Lake Superior Indians was a cancer drug. A concoction of plant extract, zinc chloride, flour, and water, copied after these native Americans, was ultimately used in a London hospital for treatment of breast cancer and received claims of remission and cures. The alkaloids in the latex, sanguinarine and chelerythrine, have been shown to act on special types of carcinomas and sarcomas, especially those of the nose and external ear.
Garlic (Allium sativum) has been mentioned as a cancer-suppressing agent because there have been reports of low incidence of cancer in regions where garlic is heavily eaten, and several researchers have reported that malignancies have been reduced when garlic was eaten. Garlic contains the sulfurous compound allicin (allylthiosulfuric allyl ester) as well as the garlic enzyme alliinase, and alliinase has been used to stop tumor growth in rats.
Wherever a plant chemical shows potential as a cancer fighter, it also provides researchers with new ideas on a type of compound to investigate further. The nice feature about plants is that they produce strange chemicals in abundance, chemicals that are very difficult for chemists to synthesize. There are a large number of known compounds with potential biological activity, but tens of thousands of species have never been sampled. The potential for finding anticancer drugs in unstudied plant species is intriguing, and this thought is on the minds of biologists who are trying to preserve natural tropical forests, which are being cut down so rapidly that species are being wiped out before they can be studied for chemicals.