1. Taxus brevifolia, also known as Pacific yew or western yew, is an evergreen tree or shrub native to western North America. 2. The bark and leaves of T. brevifolia contain the compound taxol, which was isolated in 1966 and shown to be effective against various cancers through microtubule stabilization. 3. While taxol demonstrates antineoplastic properties, its administration can cause undesirable side effects like neutropenia, peripheral neuropathy, and hypersensitivity reactions due to the vehicle used for delivery. Further research focuses on less toxic alternatives and targeted delivery methods.

1. Taxus brevifolia
Ben Merritt
-Biology, Chemistry, and
Pharmacology

2. Taxus
(Taxaceae)
- Evergreen trees or
shrubs; not resinous or
aromatic
Roots – fibrous, woody
Leaves – needles, persist for several years
(evergreen), spirally arranged (alternate),
resin canals may be present or absent
Bark – scaly or
fissured
-6-10 species ---
mostly unique
because of
geographical location

3. Taxus Growth Forms
T.
chinensis
T. bacata“Repandens”
T. bacata“Little Gem”
T. brevifolia
var. reptaneta

4. Taxus
Seeds – one per “cone,”
surrounded by fleshy aril
Pollen Cones – produced annually,
axillary, globose/ovoid
- Reproductive Structures
Seed Cones – 1-2 ovules,
axillary
T. cuspidata
- Aril is edible but seeds are toxic

5. T.
brevifolia
Anatomy-shrub/small tree
15-25m tall (200y
to mature)
-dioecious
-bark scaly;
outer scales
purplish/brown
-branches
horizontal/droopi
ng
-vegetative
reproduction
common
-inner scales
reddish/purp
le
-leaves 1-2cm x
1-4mm
-epidermal cells
mostly taller than
wide
-seeds mature
late summer/fall

6. Habitat
-Western NA – Alaska south to
Montana, Idaho and California
- Lives in moist areas
around river banks,
ravines
-Sea-level to 2200m
-May grow in
sun or shade
(needs
acclimation
period)

7. Common Names
The only common names seem to be
“Pacific Yew” and “Western Yew.”
- “yōl’-kō” in Concow
language (CA)

8. Latin Name
Taxus brevifolia (Nutt.)
brevi - = short, abbreviated
-folia = foliage; leaves
↵1. Loanword of
Scythian
(Iranian) origin;
means simply
“yew” in Latin
2. From the
Greek, meaning
“bow”; origin of
word “toxic”

9. Traditional
Uses
-Was sometimes used in
Native American
(Algonquin) smoking
mixtures called
kinnikinnick
-Needles of Taxus with uva-
ursi plant said to produce
“too strong of an effect”
-Wood was used by
Native American
tribes to make bows
-Used similarly
by the ancient
Greeks/Roman
s – considered
toxic

10. Modern Uses
-Originally found to
have cytotoxic
effects on cancer
cells (antineoplastic)
-Less toxic than
other species, most
taxol
Used on a variety of cancers
(breast, ovarian, lung, colon,
leukemia)
-Often 24-h infusion every
few weeks

11. Parts used
Primarily the bark
and leaves (active
constituents in
phloem)
-Was initially tested
against KB cells (HeLa
derivatives); have
carcinoma and papilloma
cancers
Order of potency (extract)
stem > bark > root > needles > wood
>twigs
-Needles first require non-
polar wash to remove fats
(then CO2, or other)
T.
cuspidata

12. Constituent
s
- Taxol – Isolated first in
1966 by Wall and Wani
(0.02%, dried bark)
Contains variety of
Taxanes – taxol
most active

13. Mechanism of
Action
Microtubule (MT) stabilization
-Beta-tubulin
binding only
-Promotes assembly,
discourages depolymerization
-Prevents mitosis, eventual cell
death

14. Undesirable Effects
of Taxol
Administration
(Long-term)
Causes build-up of
MT’s
Effects rapidly-
dividing cells – gut,
bone marrow,
lymphocytes
-Hypersensitivity (allergic
reaction)
-Mostly due to vehicle
(cremophor) – some
use albumin
-Peripheral Neuropathy
(doses greater than
170mg/m2
) – also may
result from cremophor
-Neutropaenia
-Problems with heart
(arrythmia, bradycardia)
-Vomiting
-Mucositis (dig.,
painful)
-Dysphagia

15. Isolation/Synthe
sisFrom the bark
(0.01-0.02%):
MeOH, then
methylene
chloride/H20 (or
chloroform)
From the needles
(0.025-0.044%):
Hexane pre-wash (waxes,
lipids)
- [ ] in bark rises
over summer
- Concentration
increases in plant
material after
letting sit for a
week or two
Hauser Chemical used
15,000lb of bark for 1kg
of taxol (0.015%)
Semi-synthetic
route (80%)
10-deacetlybaccatin III
Total synthesis
possible

16. Other Methods
of Isolation
Plant Cell
Fermentation:
Grow Taxus calluses
in aqueous media,
extract taxol
(chromatography,
crystallization)
-Bristol-Myers Squibb
Endophytic Fungi?
-Taxomyces andreanae
Original study –
(1993)
-15-20% of taxanes is
taxol
-24-50ng/liter
-May require
precursors
Later study – (2013)
-Not found to have
homologous
genes/evidence of
trans-kingdom gene
transfer
- Thought to remain in
membrane after

17. The Future
Taxol and related taxanes are useful in the
treatment of cancer, but they have many
terrible side effects.
Further research should be centered around:
1. Molecules with less toxic effects
2. Specific cell targeting (work is being done
with IG)
3. Better vehicles for administration
(albumin, pro- drug)

18. • ATCC. “KB (ATCC®
CCL-17TM
).” <http://www.atcc.org/products/all/CCL-17.aspx> May 1 2014.
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