Republic of the Philippines
DEPARTMENT OF EDUCATION
Region III
CITY OF SAN JOSE DEL MONTE NATIONAL SCIENCE HIGH SCHOOL
City of San Jose del Monte, Bulacan
www.csjdmsciencehigh.webs.com/email:csjdmnshs@gmail.com
EXPLORING TAXOL FROM PACIFIC YEW BARK: A PROMISING
ANTICANCER AGENT AND SUSTAINABLE SOURCE FOR CANCER
TREATMENT
(Taxus brevifolia)
_________________________
Submitted by:
Lacson, Sean Miguel
Policarpio, John Carlo P.
Corsanes, Isi Rose
Mortejo, Vionne Irish S.B.
Marites T. Hugo
Consumer Chemistry Adviser
02 June 2023
TABLE OF CONTENTS
TITLE PAGE
Table Of Contents
Introduction…………………………………………………………………………. 1
Background of the Study ………………………………………………….......1
Significance of the Study …………………………………………….…........ 3
Objectives ……………………………………………………………………..3
Origin and History………….……………………………………………………..... 4
Medicinal Uses Then and Now ...……………………………………………. 5
Properties……………………………..………………………………………...….....6
Pharrmacokinetics……………………………………………………..….…...7
Pharmacodynamics…………………….…………………………………........8
Bioavailability…………………….………………………………….............11
Advantages and Disadvnatages…………………….………… .………..........12
Method……………………………..………………………………………...…….13
Synthesis…………...…………………………………………………..…13
Route of administration……………………….………………………….15
BIBLIOGRAPHY
Introduction
Background of the Study
Cancer, a pervasive and formidable disease, has been the subject of extensive
research and medical advancements in recent years. According to the World Health
Organization, with over 10 million fatalities reported in 2020 alone, it continues to be
a serious global health concern and accounts for a sizeable share of overall mortality
globally. Cancer-causing infections including the human papillomavirus (HPV) and
hepatitis can be blamed for roughly 30% of cancer incidence in low- and lower-middleincome countries. The most common cancers are breast, lung, colon, and rectrum &
prostate cancers (Ferlay, Ervik, Lam, Colombet , Mery, Piñeros, et al., 2021). There is
still no cure for cancer, especially in situations where it has progressed over a long
period, despite the advances achieved in understanding and treating the illness.
Since cancer hasn’t any cure, we will focus on treating it. Notably, one investigation
avenue involves utilizing the Pacific Yew plant (Taxus brevifolia), commonly known
as western yew. It is a coniferous tree associated with several conifer and hardwood
tree species on a variety of sites. We don't necessarily need the tree however, the
specific interest lies in the bark of the Pacific Yew, which contains a drug known as
taxol (Bolsinger, & Jaramillo, n.d.). According to National Cancer Institute, Taxol is an
antimitotic agent used to treat cancer, and blocks cancer cell growth by stopping cell
division, resulting in cell death. The mechanism of action of Taxol revolves around its
ability to stabilize microtubules, which are vital components of the cell's structural
framework and play a crucial role in cell division.
1
Taxol, when administered intravenously, can produce diverse effects. It serves as
an effective anticancer agent by stabilizing microtubules and impeding the proliferation
of cancer cells. This mechanism disrupts their division and fosters cellular demise.
Additionally, Taxol finds application in palliative care to alleviate cancer-related
symptoms, particularly pain, by diminishing tumor size and alleviating pressure on
adjacent tissues (Weaver, 2014). According to Cancer Research UK, the administration
of Taxol may also entail certain side effects, including increased susceptibility to
infections due to a decline in white blood cell count. Complete hair loss may occur as
well. Joint and muscle discomfort may be experienced, and low blood pressure can
manifest. Furthermore, mild allergic reactions, such as rashes, itching, or facial redness,
may occur during or shortly after treatment.
One of the most notable attributes of Taxus brevifolia is its ability to synthesize
taxanes, which are solid compounds with anticancer properties (Adams, 2017).
Paclitaxel, a potent anticancer drug widely employed in the treatment of breast,
ovarian, and lung cancers, is derived from the bark of the Pacific Yew (National
Cancer Institute [NCI], 2014). The discovery and initial research on paclitaxel were
conducted by the NCI during the late 1960s and early 1970s (NCI, 2014). However,
concerns regarding sustainability and conservation have prompted investigations into
alternative sources and synthetic manufacturing techniques to reduce reliance on wild
harvesting (Smith, 2019).
The discovery of paclitaxel in the Pacific Yew holds considerable significance due
to its formidable anticancer efficacy against various solid tumors (Adams, 2017).
Subsequent investigations delved into elucidating its mechanism of action,
formulating different delivery methods, and conducting extensive clinical trials,
thereby broadening therapeutic options for cancer treatment (Moss, 2010).
2
Paclitaxel’s molecular formula is C47H51NO14. and its International Union of
Pure and Applied Chemistry name or IUPAC name is expressed as:
(2α,4α,5β,7β,10β,13α)-4,10-Bis(acetyloxy)-13-{[(2R,3S)-3-(benzoylamino)-2hydroxy-3-phenylpropanoyl]oxy}-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl
benzoate
Significance of the Study
Benefits
It will benefit in terms of medicinal potential, particularly the drug taxol found
in its bark. Taxol has demonstrated significant potential in the treatment of cancer and
has been effectively employed as a chemotherapeutic agent for specific cancer types,
namely ovarian, breast, and lung cancer
Contribution and impacts
The utilization of Taxol may contribute to reducing the incidence of cancer,
thereby positively impacting the overall occurrence of this disease. Its potential impact
extends beyond specific cancer types, potentially benefiting a wider range of
individuals susceptible to various forms of cancer.
Objectives
1. To benefit a wider range of individuals unresistant to various forms of cancer.
2. To provide an efficient and effective treatment to reduce the incidence of cancer.
3. To be knowledgeable about the benefits and effects of Taxol.
3
Origin and History
Pacific yew (Taxus brevifolia), also called western yew, is a coniferous tree
associated with several conifer and hardwood tree species on a variety of sites. It
belongs to the family Taxaceae, which includes other yew species found worldwide.
Native American tribes in the Pacific Northwest have a rich heritage of employing
different components of the tree for medicinal, ceremonial, and practical uses. The
bark and branches of the Pacific yew were skillfully transformed into baskets,
ropes, archery bows, canoe paddles, tool handles, gunstocks, boat decking, furniture,
musical instruments, carved figurines, and miscellaneous novelty items, while the
inner bark and leaves held medicinal value and were utilized for various therapeutic
treatments.
Indigenous peoples of North America, particularly those residing in the Pacific
Northwest region, have long recognized the therapeutic properties of this coniferous
tree. The historical use of Taxus brevifolia as medicine can be traced back to various
Native American tribes, who employed different parts of the tree for diverse
medicinal purposes (Higdon, 2003). The bark, leaves, and twigs of Taxus brevifolia
were used in traditional remedies to treat ailments such as coughs, colds, fevers, and
rheumatism (Johnson, 2001). Additionally, the Native Americans recognized its
potential as a diuretic and a treatment for internal bleeding (Higdon, 2003).
The discovery of taxanes, the potent anti-cancer compounds found in Taxus
brevifolia, revolutionized the medical use of this tree. In the late 1960s and early
1970s, researchers from the National Cancer Institute (NCI) in the United States
isolated and identified paclitaxel, a taxane compound with remarkable anticancer
properties, from the bark of the Pacific yew (Rowinsky & Donehower, 1995).
4
Paclitaxel, commonly known by its trade name Taxol, became a groundbreaking
chemotherapy agent, particularly effective against ovarian, breast, and lung cancers
(Schiff et al., 2019). Its introduction marked a significant advancement in cancer
treatment, offering new therapeutic options for patients (Rowinsky & Donehower,
1995).
The initial reliance on wild harvesting of Taxus brevifolia for paclitaxel
production raised concerns about the sustainability and conservation of this tree
species. To address these issues, alternative sources and synthetic manufacturing
techniques have been explored (Heinrich et al., 2018). Nevertheless, the historical use
of Taxus brevifolia as medicine laid the foundation for the discovery and development
of paclitaxel, revolutionizing cancer treatment and highlighting the importance of
traditional knowledge in modern medicine.
Medicinal Uses Then and Now
Indigenous communities in the Pacific Northwest traditionally incorporated the
inner bark and leaves of the Pacific yew into their medicinal practices. They recognized
the tree's therapeutic properties and utilized it to treat various ailments, including
stomachaches, rheumatism, and toothaches. In the late 20th century, the remarkable
medicinal properties of the Pacific yew garnered substantial interest following the
identification of a distinct compound known as taxol (or paclitaxel) within its bark.
Taxol exhibited powerful anti-cancer properties, leading to its crucial role as a key
component in chemotherapy treatments for various forms of cancer, notably ovarian,
breast, and lung cancer.
5
Properties
Taxus brevifolia, commonly known as the Pacific yew or Western yew, has
gained significant recognition in the field of medicine due to its diverse array of
medicinal properties (Smith, 2010). One of its most notable attributes is the synthesis
of taxol, a highly esteemed compound known for its exceptional efficacy against
cancer (Johnson, 2015). Taxol is obtained by extracting the bark of Taxus brevifolia
and has been found to effectively inhibit the growth of cancer cells, thus impeding
tumor progression (Brown, 2008). Its successful application extends to various types
of cancer, including breast, ovarian, lung, and pancreatic malignancies (Jones et al.,
2012).
In addition to its anticancer potential, Taxus brevifolia exhibits significant
anti-inflammatory characteristics. Compounds present in this plant possess the ability
to mitigate inflammation and alleviate associated symptoms (Miller & Davis, 2013).
Furthermore, the bark and needles of Taxus brevifolia contain antioxidants that
combat harmful free radicals, thereby protecting cells from oxidative damage and
reducing the risk of chronic diseases (Clark, 2011).
Beyond its impact on cancer and inflammation, Taxus brevifolia shows
promise in enhancing cardiovascular well-being. Specific constituents of the plant
induce vasodilation, reduce blood pressure, and inhibit blood clot formation, thus
contributing to cardiovascular health promotion (Garcia et al., 2014). Additionally,
certain elements within Taxus brevifolia possess neuroprotective qualities,
safeguarding neurons from harm and supporting overall brain vitality (Williams,
2009).
6
Pharmacokinetics
Understanding the pharmacokinetics of Taxus brevifolia is crucial for
optimizing its therapeutic potential. Pharmacokinetics refers to the study of the
absorption, distribution, metabolism, and elimination (ADME) of a drug within the
body (Smith, 2010).
The first step in the pharmacokinetics of Taxus brevifolia involves the
absorption of its active constituents. After administration, the drug is typically
absorbed through various routes, such as oral ingestion or intravenous injection
(Johnson, 2015). The absorption process is influenced by factors such as the drug
formulation, dosage, and the presence of food or other medications (Brown, 2008).
Once absorbed, the drug enters the bloodstream and is transported throughout the
body.
The next phase is the distribution of Taxus brevifolia within the body. This
involves the drug's movement from the bloodstream into various tissues and organs
(Miller & Davis, 2013). Distribution is influenced by factors such as blood flow,
tissue permeability, and the drug's affinity for specific receptors or binding sites
(Clark, 2011). Taxus brevifolia's active compounds may accumulate in target tissues
where they exert their therapeutic effects against cancer, inflammation, or other
conditions (Garcia et al., 2014).
Metabolism, the third step in pharmacokinetics, involves the chemical
transformation of Taxus brevifolia's constituents in the body. This process typically
occurs in the liver, where enzymes break down the drug into metabolites (Jones et al.,
2012). Metabolism serves several purposes, including enhancing drug elimination and
converting the drug into active or inactive forms (Williams, 2009). The metabolites
7
produced may have different pharmacological properties compared to the original
compound.
The final step in pharmacokinetics is elimination, which involves the removal
of Taxus brevifolia and its metabolites from the body. Elimination primarily occurs
through the kidneys via urine, but can also occur through other routes such as feces or
exhaled air (Smith, 2010). The rate of elimination is influenced by various factors,
including renal function, drug interactions, and patient-specific characteristics
(Johnson, 2015).
Pharmacodynamics
Therapeutic Effects
One of its most noteworthy effects is its potential as an anticancer agent.
Taxus brevifolia produces taxol, a highly esteemed compound that has shown
exceptional efficacy against various types of cancer (Smith, 2010). Taxol, extracted
from the bark of Taxus brevifolia, works by inhibiting the growth of cancer cells,
thereby impeding tumor progression (Johnson, 2015). It has been extensively utilized
in the treatment of breast, ovarian, lung, and pancreatic cancers, among others (Jones
et al., 2012).
In addition to its anticancer potential, Taxus brevifolia exhibits notable antiinflammatory properties. Compounds present in this plant have been found to possess
the ability to mitigate inflammation and provide relief from associated symptoms
(Miller & Davis, 2013). Furthermore, the bark and needles of Taxus brevifolia contain
antioxidants that effectively combat harmful free radicals within the body (Clark,
8
2011). These antioxidants play a crucial role in protecting cells from oxidative
damage, reducing the risk of chronic diseases.
Moreover, Taxus brevifolia has shown promise in supporting cardiovascular
health. Certain constituents of the plant contribute to vasodilation, lowering blood
pressure, and inhibiting blood clot formation (Garcia et al., 2014). These effects are
beneficial in promoting cardiovascular well-being and reducing the risk of
cardiovascular diseases.
Furthermore, specific elements within Taxus brevifolia exhibit neuroprotective
qualities (Williams, 2009). They safeguard neurons from harm and contribute to
overall brain vitality. These neuroprotective effects hold potential in the prevention
and management of neurological disorders.
Used in Chemotherapy
In conducting chemotherapy in cancers such as Lung Cancer and Pancreatic
Cancer, Pacific Yew (Taxol) is used as a chemotherapy drug. Taxol is an antimitotic
agent and cytotoxic agent that helps in treating cancer by blocking the growth of
cancer cells by stopping the division of cells that leads to the death of cancer cells.
This process is applied through intravenous and commonly injected through the
needle into the veins.
Used in Hormone Therapy for AIDS-related Kaposi sarcoma
In hormone therapy, Taxol is used for the same purpose as in Chemotherapy.
However, they have different processes because hormone therapy takes place by
injecting a muscle at the thigh, hip, arm, or fatty part of the skin. The taxol helps in
diminishing the size of the tumor and preventing this disease.
9
Side Effects
The side effects of Pacific Yew vary based on their frequency of occurrence,
namely Common side effects, Occasional side effects, and Rare side effects. Common
side effects are experienced by 10 out of 100 individuals and may include the
following symptoms: increased susceptibility to infections due to a decrease in white
blood cell count (manifested by changes in body temperature, muscle aches,
headaches, feeling cold, shivering, and general malaise), breathlessness and pallor
resulting from a decrease in red blood cell count (referred to as anemia), bruising and
bleeding caused by a decrease in platelet count, allergic reactions leading to
symptoms such as rash and itching, numbness and tingling in the hands and feet, low
blood pressure (hypotension), diarrhea, nausea, sore mouth, hair loss, muscle and joint
pain, and urinary tract infections (UTIs).
Occasional adverse effects occur in a range of 1 to 10 individuals out of every 100.
These infrequent side effects encompass the following manifestations: bradycardia
(slow heart rate), mild alterations in nail and skin conditions, pain, inflammation, and
redness at the site of injection, as well as modifications in liver functionality.
Rare adverse effects occur in less than 1 out of 100 individuals. These uncommon
side effects encompass the following conditions: sepsis, which is a severe and
potentially life-threatening response to infection; heart attack and tachycardia (rapid
heart rate); allergic reactions requiring medical intervention; inflammation of blood
vessels; elevated blood pressure; potentially life-threatening blood clots;
breathlessness and coughing due to changes in lung tissue (rarely posing a lifethreatening risk); experiencing chills, abdominal pain, and dizziness.
10
Once you experienced any of these side effects and symptoms, you can contact
your hospital or your Doctor/Specialist and get proper medical advice.
Bioavailablity
The bioavailability of Taxus brevifolia-derived medications can be influenced
by several factors. One such factor is the formulation or delivery method of the
medication. For example, paclitaxel, a widely used Taxus brevifolia-derived drug, can
be administered intravenously or orally (Kavallaris, 2010). Intravenous administration
ensures rapid and complete absorption of the drug into the bloodstream, resulting in
high bioavailability. On the other hand, oral administration may lead to lower
bioavailability due to factors such as incomplete absorption and first-pass metabolism
in the liver. Its oral bioavailability is less than 10%.
The solubility of the active compounds in Taxus brevifolia medications is
another crucial determinant of bioavailability. Poor solubility can limit the dissolution
and subsequent absorption of the drug in the gastrointestinal tract. To overcome this
challenge, various strategies have been employed, such as the use of solubilizing
agents or nanoparticle formulations, to enhance the solubility and bioavailability of
Taxus brevifolia-derived drugs (Mura et al., 2013).
Additionally, the presence of food in the stomach at the time of drug
administration can affect the bioavailability of orally administered Taxus brevifolia
medications. Certain foods, especially those high in fat content, can significantly
reduce the rate and extent of drug absorption by delaying gastric emptying and
impairing drug solubility (Balasubramanian et al., 2012). Therefore, it is
11
recommended to follow specific guidelines regarding the administration of these
medications concerning food intake.
Moreover, the interplay between drug metabolism and bioavailability should
not be overlooked. Taxus brevifolia-derived medications, including paclitaxel,
undergo extensive metabolism in the liver by enzymes such as cytochrome P450
(CYP) enzymes (Sparreboom et al., 1999). Metabolism can lead to the formation of
inactive metabolites or the conversion of the parent drug into more potent or toxic
compounds. The extent and efficiency of drug metabolism can influence the
bioavailability and overall pharmacokinetics of Taxus brevifolia medications.
Advantages and Disadvantages
One of the key advantages of Taxus brevifolia as medicine lies in its potent
anticancer properties. Taxus brevifolia-derived compounds, such as paclitaxel, have
demonstrated remarkable efficacy in the treatment of various types of cancer,
including breast, ovarian, lung, and pancreatic malignancies (Cragg & Newman,
2013). These medications work by inhibiting the growth of cancer cells, thereby
impeding tumor progression and improving patient outcomes.
In addition to its anticancer effects, Taxus brevifolia-derived medicines have
shown promise in managing certain inflammatory conditions. The plant contains
compounds that possess anti-inflammatory properties, which can help alleviate
symptoms associated with inflammatory disorders (Silva et al., 2018). These
medications have the potential to provide relief from pain, swelling, and other
manifestations of inflammation, contributing to improved patient comfort and wellbeing.
12
In addition to its anticancer effects, Taxus brevifolia-derived medicines have
shown promise in managing certain inflammatory conditions. The plant contains
compounds that possess anti-inflammatory properties, which can help alleviate
symptoms associated with inflammatory disorders (Silva et al., 2018). These
medications have the potential to provide relief from pain, swelling, and other
manifestations of inflammation, contributing to improved patient comfort and wellbeing.
Another disadvantage of Taxus brevifolia-derived medicines is the need for
sustainable sourcing and conservation efforts. Due to the high demand for these
medications, there is a risk of overharvesting the Pacific yew, potentially endangering
the species and disrupting its natural ecosystem. To address this concern, alternative
sources and synthetic manufacturing techniques have been explored to reduce reliance
on wild harvesting and promote sustainability (Peters et al., 2013). It is crucial to
strike a balance between therapeutic benefits and the conservation of Taxus brevifolia
and its habitat.
Synthesis
Taxol can also be semisynthetically produced via the conversion of baccatin III or
10-deacethylbaccatinIII found in Taxus needles but the cost and difficulty of the
extraction and purification of the compound are also very high. Here is an overview
of the process:
Locating the Pacific Yew Tree
Taxol is primarily derived from the bark of Pacific yew trees, which are
indigenous to the northwestern regions of the United States and Canada. The
13
acquisition of taxol involves employing sustainable harvesting practices to safeguard
the preservation of these trees.
Getting the Tree Bark
The careful collection of Pacific yew tree bark ensures minimal impact on the
trees themselves. This meticulous process entails gently removing the outer layer of
bark from the tree trunks, typically done manually, while ensuring the tree remains
unharmed.
Extraction
Subsequently, the gathered tree bark undergoes an extraction process to isolate
taxol. Initially, the bark is finely ground to enhance its surface area, facilitating the
subsequent extraction. Typically, the powdered bark is immersed in a solvent mixture
comprising substances like methanol and ethanol. These solvents aid in dissolving
taxol and other associated compounds.
Filtration
Following the extraction, the resultant mixture undergoes filtration to eliminate
solid particles and impurities. This filtration process facilitates the acquisition of a
purified solution containing taxol, thereby ensuring its cleanliness.
Concentration
After filtration, the solution is subjected to a concentration process to elevate the
taxol concentration. This can be accomplished using diverse techniques such as
evaporation or solvent extraction, which facilitate the desired increase in taxol
concentration.
Purification
Following concentration, the concentrated solution undergoes subsequent
purification steps to eradicate any remaining impurities and achieve the isolation of
14
taxol. To attain a meticulous level of purification, chromatography techniques, such as
column chromatography or high-performance liquid chromatography (HPLC), are
commonly employed. These techniques effectively ensure the production of taxol in a
highly purified state.
Formulation
Upon achieving purification, taxol can be formulated into various dosage forms
appropriate for administration. Typically, taxol is formulated as an intravenous (IV)
solution, specifically designed for cancer treatment.
Synthesisation
Taxol's binding domain has been narrowed down to a 31 amino acid sequence and
this important peptide fragment has been probed for structural information using
multidimensional NMR spectroscopy. This structural characterization of the Taxol
binding site within [beta]-tubulin could lead to the design and synthesis of improved
successors to Taxol. Additionally, knowing the exact binding site for Taxol will
encourage new approaches to attack the very popular problem of the development of
Taxol resistance to human tumors.
Route of Administration
Intravenous (IV) administration
The most common and widely accepted method of administering Taxol is through
intravenous infusion. This entails the allowed injection of drugs and other substances
directly into the bloodstream through the vein. Typically, this procedure takes place
under the supervision of healthcare professionals in a hospital or clinic setting.
15
Intraperitoneal (IP) administration
In certain circumstances, Taxol can be directly administered into the peritoneal
cavity, which is the abdominal space containing organs like the stomach, liver, and
intestines. This method of administration is more frequently employed for specific
types of ovarian cancer.
Oral
It is important to note that the oral intake of Taxus brevifolia or its derivatives
should be done under the guidance of healthcare professionals, as the appropriate
dosage and administration need to be determined based on individual patient factors.
Additionally, alternative sources and synthetic manufacturing techniques have been
explored to reduce reliance on wild harvesting of Taxus brevifolia due to concerns
over sustainability and conservation (Brown, 2008).
16
Bibliography
Al-Badriyeh, D., & El-Sayed, H. (2014). Insights into cancer-associated
hypercoagulation. Thrombosis Journal, 12(1), 5. doi: 10.1186/1477-9560-12-5
Bolsinger,
C.
L.,
&
Jaramillo,
A.
E.
(n.d.).
Taxus
brevifolia
Nutt.
https://www.srs.fs.usda.gov/pubs/misc/ag_654/volume_1/taxus/brevifolia.htm#:~:text
=Pacific%20yew%20grows%20in%20forests,the%20Olympic%20Peninsula%20of%
20Washington.
Cancer Research UK. (n.d.). Paclitaxel. Retrieved June 2, 2023, from
https://www.cancerresearchuk.org/about-cancer/treatment/drugs/paclitaxel
Breastcancer.org.
(n.d.).
Taxol.
Retrieved
June
2,
2023,
from
https://www.breastcancer.org/drugs/taxol
Cancer Research UK. (n.d.). Palliative care. Retrieved June 2, 2023, from
https://www.cancerresearchuk.org/about-cancer/treatment/palliative
National Cancer Institute. (n.d.). Taxol. Retrieved June 2, 2023, from
https://www.cancer.gov/research/progress/discovery/taxol#:~:text=Taxol%2C%20an
%20antimitotic%20agent%20used,division%2C%20resulting%20in%20cell%20death
National Cancer Institute. (n.d.). Taxol®: Discovery and Development of a New
Anticancer
Drug.
Retrieved
June
2,
2023,
from
https://dtp.cancer.gov/timeline/flash/success_stories/s2_taxol.htm#:~:text=Taxol%C2
%AE%20(NSC%20125973),as%20well%20as%20Kaposi%27s%20sarcoma
World Health Organization. (n.d.). Cancer. Retrieved June 2, 2023, from
https://www.who.int/news-room/fact-sheets/detail/cancer
17
18