Medical Significance

Taxus brevifolia has grasped the attention of the medical community because it contains the most promising new cancer drug to come along in years. This anticancer agent, known as taxol, can be extracted from the bark of the Pacific yew. It is a chemotherapeutic drug that has been shown to be extremely effective against ovarian cancer and may assist in the treatment of other forms of the disease. Like all such drugs, taxol inhibits the correct expression of the genetic code. In fact, taxol actually inhibits the production of daughter cells by halting the mitotic process. Generally, taxol freezes the parent cancer cell in a mitotic stage before it can fully differentiate into its daughter cells. In order for the daughter cells to form, a microtubule spindle fiber must form, the chromosomes must separate and the tubulin that composes the microtubules of the spindle must decompose. When taxol is introduced into the dividing cell, it binds to the tubulin molecule in the microtubules and effectively makes these tubules indestructible. The cell therefore cannot complete mitosis and is frozen in this intermediate stage. This consequently will halt the rapid growth of cancerous tumors and leave malignant cells benign.

Image from Lawrence and Jenkins, 1992
Taxol, also known as paclitaxel, is classified as an unusual diterpene having a taxene skeleton. This complicated molecule is an exciting new possibility in the pharmacologist's struggle to find the perfect anticarcinogen. The mechanism in which taxol exhibits its action is rather unique. Most other anti-mitotic drugs, such as the vinca alkaloids and colchicine, depolymerize the mitotic spindle. They actively break it down so the cell cannot replicate itself. With drugs of this type, cancer cells cannot replicate while the drug is present in the body, but once the drug is removed from the cell, it can once again replicate. Taxol, on the other hand, actually induces polymerization of the microtubule spindle fibers to a point at which they are so stable that they cannot be broken down and the cell is effectively permanently frozen in the process of dividing. Taxol and its analogues are the only such compounds that act as mitotic spindle stabilizers.

Like DNA, microtubules are ubiquitous cellular components. Microtubules are in dynamic equilibrium with their basic protein components, the tubulin dimer. Whereas most anti-mitotic agents seem to shift this equilibrium back towards the soluble tubulin dimers, taxol shifts the equilibrium toward stabilized microtubule assembly. Basically, taxol does not bind to free tubulin dimers, but rather it preferentially binds to tubulin dimers that are components of the microtubule and effectively locks them into the microtubule conformation. Taxol has one other general effect. In concentrations as low as 0.05 micromoles/L, taxol seems to create the perfect cellular environment for pushing the aforementioned equilibrium towards microtubule assembly. Remarkably, taxol-treated microtubules are stable even after treatment with calcium or low temperatures, conditions that usually promote disassembly.

For taxol to be clinically useful, it must be administered in concentrations ranging from 0.1-10 micromoles/L. These concentrations of taxol produce several dramatic effects in microtubular organization. First of all, cells treated with taxol organize the arrays of disorganized microtubules into parallel bundles. Secondly, in addition to freezing the normal, microtubular, mitotic spindle, the taxol-treated cell often contains other centers of microtubular organization known as asters. In normal cells, centrioles organize most of the microtubules into the mitotic spindle. In addition, centrioles produce asters, which are smaller microtubular radiations that anchor the centriole within the cell's cytoplasm. In the taxol-treated cell, several more asters are formed at various locations within the cell serving to further strengthen the cell's structure and preventing, in a different manner, cell separation. These properties are what make taxol such a special compound.

Cancer is an inevitable disease. So long as people live, cancers will occur. There will never be a vaccine that someone can invent in order to prevent one from ever getting cancer. The disease is a mutation, and mutations are impossible to prevent because of their inherent random nature. While taxol may not be the end all cure for cancer, it is definitely a significant move towards a highly effective treatment. To this we owe all the thanks to a simple little yew tree called Taxus brevifolia.

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