Method could also be used for other drugs
by Helen Tunnicliffe
Paclitaxel was originally isolated directly from the bark of Taxus brevifolia
RESEARCHERS have found a way to produce the widely-used cancer drug paclitaxel (Taxol) from a culture of stem cells, which they say could make the drug cheaper.
The work was carried out by Korean firm Unhwa Biotech and led by Gary Loake, a biology professor at the University of Edinburgh. Paclitaxel is used in the treatment of lung, ovarian, breast, head and neck cancer but its production is expensive.
Paclitaxel was originally isolated directly from the bark of Taxus brevifolia, the Pacific yew, but concerns were raised over the sheer numbers of trees required to make just a very small amount. Bristol–Myers Squibb, which makes paclitaxel, then developed a way to produce paclitaxel using plant cell fermentation technology, in which cells from yew twigs and needles are cultured in bioreactors to produce a more-abundant precursor to paclitaxel which is then chemically modified to attach functional groups and produce the drug.
The cells used in the process are so-called “dedifferentiated” plant cells. The differentiated cells from the needles and twigs do not naturally divide and must therefore be reactivated, or dedifferentiated, using plant hormones. This process however, can cause genetic damage, meaning that cells are unstable and grow inconsistently. They also do not last very long, so they must be regularly replaced. Another problem is that the chemical process to produce paclitaxel from the precursor produces harmful by-products.
Undifferentiated cambial meristematic cells do not require such reactivation. They are the dividing stem cells formed deep inside the plant’s meristem and go on to form differentiated cells. Loake and the team isolated cambial meristematic cells from yew and cultured them instead. Loake tells tce that because the cells do not have to be treated to make them divide, they do not have the genetic damage of dedifferentiated cells and can therefore grow consistently and virtually indefinitely, providing conditions such as hormone levels are kept right. The process also produces paclitaxel directly, removing the need for the chemical modification step.
Loake and his colleagues also cultured stem cells from other plants, including tomato, tobacco and ginseng, which produces a group of compounds called ginsenosides which have various potential clinical applications. The team are therefore hopeful their methods could be more widely-applicable.
"Plants are a rich source of medicine – around one in four drugs in use today is derived from plants. Our findings could deliver a low-cost, clean and safe way to harness the healing power of plants, potentially helping to treat cancer, and other conditions," says Loake.
Nature Biotechnology doi: 10.1038/nbt.1693