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Spindle Inhibitors: The Vinca Alkaloids

The Vinca alkaloids are a subset of drugs that are derived from the periwinkle plant, Catharanthus roseus (also Vinca rosea, Lochnera rosea, and Ammocallis rosea). It is also commonly called the Madagascar periwinkle or the rose periwinkle. While it has been historically used to treat numerous diseases, it has most recently been employed for its anti-cancer properties. The plant grows in warm regions of the world and especially in the Southern United States. The "flower" is usually pale pink with a dark violet dot in the center.(1)

All vinca alkaloids are administered intravenously (IV). After injection, they are eventually metabolized by the liver and excreted. They work in a cell-cycle specific manner, halting mitosis of affected cells and causing cell death. As stated in the introduction, the mechanism involves binding to the tubulin monomers and keeping the microtubules (spindle fibers) from forming. Although the plant has medical uses, it can produce many serious side effects if smoked or ingested.

There are four major vinca alkaloids in clinical use:

A Closer Look at the Discovery of a Spindle Inhibitor

Dr. Monroe E. Wall and Dr. Mansukh C. Wani discovered paclitaxel (Taxol®) at the Research Triangle Institute in 1967. They isolated the compound from the Pacific Yew tree (Taxus brevifolia) and tested it as an anti-tumor drug in rodents. The mechanism of action for paclitaxel was reported by scientists at the Albert Einstein Medical College in 1980. In December of 1992, the FDA approved paclitaxel for the treatment of ovarian cancer. Today the drug is used for a variety of cancers, including ovarian, breast, small-cell and large-cell lung cancers, and Karposi's sarcoma.(2) Paclitaxel is a plant alkaloid that is derived from the bark of the Pacific Yew Tree (see photo). The Pacific Yew grows in moist soils and can be found in British Columbia, Alaska, California, Idaho, Montana, Oregon, and Washington. It takes about 2g of paclitaxel (about 3-10 trees) to treat one patient. Paclitaxel is obtained via a semi-synthetic process from the English Yew tree, Taxus baccata. Both paclitaxel and Paclitaxel are administered as a series of intravenous injections.(3)

Image source: Natural Resources Canada, the Canadian Forest Service.

References for this page:
  1. Synder, Lucy. "Description and Natural History of the Periwinkle." University of Texas, Institute for Cellular and Molecular Biology. November 1997. [http://biotech.icmb.utexas.edu/botany/perihist.html]
  2. Fact Sheet: RTI's Discovery of Taxol. Research Triangle Institute. 2001. (March 2002). [http://www.rti.org/page.cfm?objectid=71215B17-D95B-46E8-8BBCA18016AFF167]
  3. Sally J. DeNardo, Gerald L. DeNardo, Arutselvan Natarajan, Laird A. Miers, Allan R. Foreman, Cordula Gruettner, Grete N. Adamson, and Robert Ivkov. "Thermal Dosimetry Predictive of Efficacy of 111In-ChL6 Nanoparticle AMF Induced Thermoablative Therapy for Human Breast Cancer in Mice." Journal Nuclear Medicine 2007 48: 437-444. [PUBMED]
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