February, 2000: Madagascar
Vinblastine and Vincristine are two alkaloids isolated from Catharanthus roseus, the rosy periwinkle from Madagascar. Alkaloids are a major class of natural products that have a physiological effect in other organisms. They characteristically contain carbon, hydrogen, nitrogen, and in many cases, oxygen. Because of their potent pharmacological effects, alkaloids are the basis for many drugs.
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Rosy periwinkle. (Photo © 1999 Erica Kipp.)
C. roseus is in the Apocynaceae family, which is composed of dicots, usually shrubs or herbs, that have either opposite or whorled entire leaves. An attractive plant, it is cultivated worldwide as an ornamental. In the 1950s, Eli Lilly and Company, while screening natural products in bioassays, discovered that a leaf extract from C. roseus could affect the progress of leukemia. As a result, the pharmaceutical company introduced anticancer drugs known as vinca alkaloids in the 1960s. Vinblastine is used to treat Hodgkin disease, a cancer of the lymphatic system, and vincristine is used to treat pediatric leukemia, which is cancer of the bone marrow and other blood-cell-producing organs.
Vinblastine and vincristine are administered by injection. Both are considered antineoplastic drugs because they impede new and abnormal growth, such as a malignant tumors. Because vinblastine and vincristine damage or destroy cells (sometimes indiscriminately) by inhibiting cell division, they are also referred to as cytotoxic. Specifically, mitosis is halted during metaphase by targeting the formation of microtubules, proteinaceous structures that are important to spindle formation in all cells. In plants, microtubules are also important in regulating cellulose accumulation in the cell wall.
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Vinca alkaloids.
Mitosis in a plant cell.
More than 80 alkaloids have been identified from plant extracts of the genus Catharanthus. Because C. roseus makes such an abundance of complex chemicals, it is both difficult and costly to extract and purify vinblastine and vincristine. But recently, the development of cell culture systems and culture techniques is making the alkaloid treatments available at a more reasonable cost, as well as increasing the potential yields.
Skilled technician removing the apical meristem from an orchid. (From Stern, Introductory Plant Biology, 8th ed., ©2000 McGraw-Hill Companies, Inc.)
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Flasks with meristematic tissue added. (From Stern, Introductory Plant Biology, 8th ed., ©2000 McGraw-Hill Companies, Inc.)
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Developed plants from meristematic tissue. (From Stern, Introductory Plant Biology, 8th ed., ©2000 McGraw-Hill Companies, Inc.)
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Cell tissue culture is a technique whereby a mass of undifferentiated cells called a callus is maintained indefinitely on an artificial medium. The tissue culture can be initiated with almost any plant part; however, best results are obtained with tissue taken from the apical meristem region. Cell differentiation occurs with proper conditions, including a medium containing hormones (such as cytokinins) and organic substances. Tissue culture has the advantage of allowing large numbers of cells to be grown in smaller spaces while maintaining sterile conditions and a controllable environment. Just compare several acres of land to the populations that can be grown (and manipulated) within a few laboratory test tubes!
References, Websites, and Further Reading
Hesse, Manfred. 1981. Alkaloid chemistry. New York: John Wiley & Sons.
Lymphoma Information Network main page
Stern, Introductory Plant Biology, 8th Edition
Chapter 2: The Nature of Life
Elements, molecules, and compounds, pp. 15-18
Chapter 3: Cells
Microtubules, mitosis, metaphase, cell cycle, pp. 38-48
Chapter 7: Leaves
Simple/entire leaves; phylotaxy, pp. 106-10
Chapter 8: Flowers, Fruits, and Seeds
Monocots and dicots, pp. 129-30
Chapter 11: Growth
Cytokinins, p. 193
Chapter 14: Plant Propagation and Biotechnology
Tissue culture and mericloning; traditional vegetative propagation; stem and leaf cuttings, pp. 238-47
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