Medical Attributes of Taxus brevifolia - The Pacific Yew

by Jay Shah, Shannon Kotch, and Paul Witt
Wilkes University
Wilkes-Barre, PA

May 2009
Taxus brevifolia, commonly known as Pacific yew, is a member of Taxaceae.  It is native to the western coast of North America, ranging from Alaska to California (USDA).  The average height of Taxus brevifolia ranges between 5 and 15 meters (Anonymous 2009a).  Pacific yew is shade tolerant evergreen tree, and it grows primarily as an understory tree in humid forested habitat in subtropical to temperate climates (Vanc & Rudolf 2008).  Taxus brevifolia plants have flat, evergreen needles and seeds surrounded by a red fleshy aril (Anonymous 2009b).

Traditional uses of yew plant included making weapons, harpoons, canoe paddles, drum frames, etc. due to its strength and toughness (Earle 2008). Yew was also used for medicinal purposes. Native Americans used yew plant to impart strength, induce perspiration, and treat internal injuries and lung diseases (Earle 2008).  The Japanese used the yew plant parts to induce abortion and treat diabetes (Anonymous 2009b). Conversely, toxicity of the extracts derived from the members of yew family has been described in ancient Greek literature (Anonymous 2009b).  Today, Pacific yew is primarily used as an ornamental tree, and commercially extracts such as paclitaxel derived from its bark are used to treat various cancers (Earle 2008; Anonymous 2009b). 

The key constituents of the Taxus plant includes diterpene alkaloids called taxanes, that are poisonous in high dosage but an effective anti-neoplastic agent when used in small doses (Scripture et al. 2006).  Paclitaxel, docetaxel and 10-deacetylbaccatin III are most notable members of the taxane family (Guéritte 2001). Bristol-Myers Squibb markets paclitaxel as Taxol® (Leary 1992).  Before 1992, publications referred to the compound under the name ‘taxol’ which is equivalent to paclitaxel (Walsh & Goodman 2002).  Docetaxel is a semi-synthetic analogue of paclitaxel derived from the needles of Taxus baccata (European yew).

Due to the widespread historical account of medicinal effects of yew plant extracts, United States Department of Agriculture (USDA) together with the National Cancer Institute (NCI) started a screening process where Pacific yew extracts were tested against two cancer cell lines, ovarian and breast cancer (Anonymous 2009b; Walsh & Goodman 2002). One such discovery resulting from the screening was Paclitaxel, a hydrophobic anti-neoplastic agent found in Taxus brevifolia which has been shown to have anticancer properties.  It is currently used to treat ovarian, breast and lung cancer (Scripture et al. 2005).  It is an active component of ethanolic extracts from the bark of the tree (Scripture et al. 2005).  Paclitaxel blocks cell division by decreasing the amount of free tubulin in cells (Bombuwala et al. 2006).

Unfortunately, the hydrophobic nature of paclitaxel hinders further research and drug preparation because it impedes rapid and efficient drug distribution in the body’s aqueous fluid system and increases exposure to macrophage activity (Neuse 2008; Lee et al 2008). Low availability of taxol and environmental concerns regarding stripping yew tree of bark have triggered research into alternative sources and production of taxol and its precursors (Miller et al. 2008; Anonymous 1987). Currently, plant cell fermentation technology is used by Phyton Biotech to produce Paclitaxel which eliminates the need for harvesting yew tree (Anonymous 2006).

Since chemical synthesis of complex diterpenes involves numerous steps with low yields, research is now concentrated on enhancing in vivo production of paclitaxel and its precursor 10-deacetylbaccatin III. Understanding the enzymatic mechanism of taxol production in pacific yew has led to better synthesis of taxol like substances in cell cultures of other Taxus species (Miller et al. 2008). One alternative is 7-xylosyl-10-deacetylpaclitaxel, isolated from Taxus chinensis, which showed high water solubility along with mitotic cell cycle arrest and apoptosis (Jiang et al. 2008).

In-vitro and in-vivo experiments conducted to test the effects of docetaxel as an anti-glioma therapeutic agent presented encouraging results when used in conjunction with biodegradable polymer (Sampath et al. 2006). Docetaxel has also been used as a palliative agent to treat neoplasms such as hormone-refractory prostate cancer. Clinical trials demonstrated that administration of docetaxel along with prednisone, a common corticosteroid, every three weeks increased survival rate, improved quality of life and reduced serum prostate-specific antigen levels (Tannock et al. 2004). Additional clinical trials on the use Docetaxel with supplementary therapeutics, for example cisplatin and oxaliplatin, to treat cancers such as metastatic gastric and gastroesophageal junction adenocarcinoma (Di Lauro et al. 2009), multiple lung metastases of hepatocellular carcinoma (Tsuchiya et al. 2009), advanced or metastatic breast cancer (Baker et al. 2009) and uterine and ovarian cancer (Gupta et al. 2009) showed promising results.

Fungal endophytes such as Taxomyces andreanae (Class Ascomycetes), have been isolated from the yew tree to produce taxol and taxol like substances (Stierle et al. 1995; Anonymous 2007). Ubiquitin promoter was used to constitutively express taxadiene synthase gene and produce taxa-4(5), 1 1(12)-diene precursor in moss Physcomitrella patens. Unlike higher plants, taxadiene didn't exhibit growth pattern inhibition due to altered diterpenoid metabolic pool, thus making it a promising alternative host for paclitaxel and its precursor biosynthesis (Anterola et al. 2009).

Side effects of paclitaxel include peripheral neurotoxicity (Scripture et al. 2006), mucocutaneous reactions such as alopecia, mucositis, hypersensitivity reactions (with erythema and urticaria), nail changes, changes occurring at intravenous sites, and radiation recall dermatitis (Cohen 2009). Some of the side effects of docetaxel use during clinical trials included asthenia, nail toxicity (Baker et al. 2009), neutropenia, hypersensitivity reactions, and fluid retention (Fossella et al. 1995; Baker et al. 2009).

Traditionally, the Pacific yew, Taxus brevifolia has been used for its wood and intrinsic versatility in treating a host of ailments. Contemporary medicine has found value in paclitaxel, a chemotherapeutic which reduces the amount of free tubulin thereby hindering mitosis of cancer cells. The limited availability of paclitaxel spurred the genesis of various semi-synthetic analogues such as docetaxel which when complexed with steroids seem to be more efficacious in treating various types of cancer. And although there are several unwanted side effects of these chemotherapeutics involving mucocutaneous and hypersensitivity reactions, the value and potential benefits of such compounds are undeniable.

LITERATURE CITED

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This paper was developed as part of the BIO 368 - Medical Botany course offered at Wilkes University during the spring of 2009. Course instructor was Kenneth M. Klemow, Ph.D. (kenneth.klemow@wilkes.edu). The information contained herein is based on published sources, and is made available for academic purposes only. No warrantees, expressed or implied, are made about the medical usefulness or dangers associated with the plant species in question.

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