Saturday, March 14, 2009

Taxol, anticancer drug from taxus family


100 years old tree of Taxus brevifolia is 6 – 9 meter in height is suitable for collection of trunk or stem bark.
Stem is having the diameter of 25 cm.
Bark is removed in May – August & bark of 3 matured tree would give 1 gm of Taxol.
Generally 2 gm Taxol is required for Cancer treatment.
Bark contains about 0.01 – 0.02% of Taxol & 0.2% of Bacatin – III.
Taxus plant i.e. Taxus brevifolia is known as “Pacific Yew” / “Yew Plant”.
In India, it is known as “Rakshala” or “Barhmi”.
The plant is known to have poisonous effect to children & animals.
Entire plant is toxic except Red Arillus of Seed.
The Bark was used in the treatment of Rheumatism, Liver disorder & UTI.
In Western Himalayas, the dilute Decoction of Bark was taken during Winter by tribal people to increase the body resistance against Cold.
Due to high tensile properties of wood, it was used to make gows & implements.
The wood has high Caloric value, so was used in Potaries.
In Europe, it was used for habges.
Dried Leaves are used in “Havan” in India.
Taxol was isolated in 1971 from T. brevifolia by Dr. Wani & it was found to be useful in Cancer treatment.
Taxol is a Diterpene.
It affects Microtubule assembly in the dividing cells & stops the production of cells.
It is useful in Murine Leukemia (of Cavity).
Also is effective against Cancer of Lung, Breast, Colon & Ovary.
For activity of drug, 4 membered Oxygen ring, 2’ OH group, 3’ NH2 group & Acyl side chain are essential.
Taxus is also Antifungal & Insecticidal.
Himalayan Yew
Taxol is a Naturally occurring Diterpenoid belonging to Taxane group of compounds present in genus Taxus.

Different species of Taxus grown in World;

Taxus baccata è European Yew
T. cuspidata è Japanese Yew
T. chineusis è Chinese Yew
T. brevifolia è Pacific Yew
T. wallichiana è Himalayan Yew
T. canadensis è Ground Hemlock / American or Canadian yew
The Genus Taxus also called Yew consists of various species out of which 4 are of Medicinal importance viz;

T. baccata
T. cuspidata
T. brevifolia
T. canadensis
FAMILY: Taxaceae
Plant is found in Temperate Forests.
It is a Small Evergreen tree, existing in under storey.
It has Dark Green, Long & Narrow shining Leaves.
Tree is found at an elevation of 7000 – 11,000 feet.
Taxane derivatives are also present in Leaves,
So, Leaves are harvested.
Therefore if Bark is taken, the Tree wood die.
In order to treat Breast & Ovary cancer è 2.5 g Taxol is required.
World – Wide Trade of Taxol is reached to US $ 1.92 billion.
World’s requirement è 700 kg / year
Current Production è 350 kg / year
Present production of Taxol is only 350 kg & demand is double, therefore conserve / propagate the plant.

RRL – Jammu has initiated programmes for conservation of Himalayan Yew, on following lines;

They have found out Taxus growing area & are trying for regeneration of plants.
They have started propagation & cultivation by new techniques.
Plants are found in Himachal Pradesh & North Eastern Himalayan region, mostly in / on inaccessible slopes.
The plants have been heavily debarked & most of damages are recent.
The plant regeneration is almost absent.
The potential areas of Taxus which were there few decades ago are now no more.

The availability of Taxane is better from the Leaves than bark.
Leaves contain small amount of Taxol.
But contain higher amount of Bacatin III.
Taxol is nowadays no more drug of choice.
Many Semisynthetics like Taxoterene shows better activity which is produced from Bacatin III.
Also, it has lesser Side Effects.

Propagation can be carried out through Stem cutting.
Cutting of the Terminal part of Axis / Twig will give 80 – 90% Rooting.
After Treatment with Indole Butyric Acid (IBA) ~ 200 ppm for 18 hours, would give better results.
The best time for planting the cuttings is November – February.

Bandages containing GA3 (Gibberellic Acid) or IBA are applied on branch / twig & then after 90 days, cuttings are transplanted.
This plant is as good as 5 years old plant.

Seeds take about 1 year to germinate.
However, Seeds are stratified & treated with Gibberellic acid (GA3).
Seeds can be cultivated in even poor soil, but water logging is harmful.
It can be planted at 40 x 40 cm distance.
Transplanting of Plant is dangerous.
Therefore plant will die due to shock of Roots.
Taxol amount is more in such plants.
Plant grows well in cool & moist places.

Collection Time è June – July for Bark & Needles (Leaves).

Leaves are dried in thin layers.
Active constituents would increase on storage for 9 days, regardless of storage temperature.
Cell culture & Biotechnology è Taxol production by this way fail to compete with the naturally cultivated plant.
Tribals called Taxus Tree “TREE OF DEATH” because in past it was believed that anybody who sleeps under this tree would go to eternal sleep forever.

Taxol affects Microtubule assembly in the dividing cells & stops the production of cells.
Inhibits Cell Migration.
Thus preventing spread of Metastatic Cancer cells.
It has also a promising role against Non – small cell;
Lung Carcinoma
Gastric Cancer
Cervical Cancer
Carcinoma of Head, Neck, Prostrate & Colon.

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