Nov 05, 2015
Extracts from some herbal remedies may make cancers more vulnerable to conventional chemotherapy drugs.
Feverfew: May enhance chemotherapy.
Plantextracts with anti-inflammatory properties may be useful in increasing the vulnerability of cancers to chemotherapeutic drugs, new research in Oncogene 1suggests.
Chemotherapy can hold diseases such as breast cancer at bay, but patients often die when tumour cells eventually develop resistance to the drugs used. Now Harikrishna Nakshatri and his colleagues from the Indiana Cancer Research Institute have delved into the herbal medicine cabinet and found compounds that inhibit the genes responsible for this resistance.
There are many genes in our cells that can cause cancer if they become active in the wrong place or at the wrong time. These include the genes responsible for encouraging cell growth and preventing cell death -- cancer is basically a form of uncontrolled cell growth.
These different groups of genes work together to encourage normal growth in healthy tissue. Such groups can all be switched on by 'transcription factors', proteins that bind to the DNA of the genes and activate them. A damaged or mutated transcription factor can cause cancerous growth by switching on all the genes that it normally regulates in a massive and uncontrolled manner.
Nakshatri had previously identified such an errant transcription factor in some breast cancers, called 'nuclear factor-kB', or 'NF-kB' for short. High levels of NF-kB have also been found in many other cancers.
Many cancer treatments stop cells dividing and growing. But Nakshatri and his team showed that NF-kB activates several cell division genes. If NF-kB levels are high enough, then the tumour cells can overcome the effects of the drugs.
As a patient undergoes chemotherapy, only the tumour cells that have high levels of NF-kB survive -- until you end up with a tumour full of NF-kB-rich cells, all resistant to the drug.
It seems clear that removing NF-kB from the picture should restore drug sensitivity. Interestingly, several traditional herbal remedies attack NF-kB. These include aspirin (from the bark of the willow tree, Salix alba), and helenalin, an extract of the native Mexican plant Smallhead Sneezeweed (Helenium microcephalum).
But many of these compounds adversely affect other chemicals in the cell. Parthenolide is an exception. An extract from the herb feverfew (Tanacetum parthenium), parthenolide has long been a traditional remedy for migraine, and it now emerges that it is a highly specific inhibitor of NF-kB.
Nakshatri and his colleagues grew cancer cells in the presence of parthenolide and a commonly used anti-cancer drug, paclitaxel or Taxol, which inhibits cell division. They found that without NF-kB, the cells were much more susceptible to paclitaxel. In fact, the researchers killed off the cancer cells using lower doses of paclitaxel that did not have harmful effects on normal cells.
Nakshatri conclude that other medicinal plants might also be used in tandem with chemotherapies where tumours are rich in NF-kB. They suggest that extracts of Barberry (Berberis), Coptis (Coptis chinensis) and Gravel root (Eupatorium purpureum), all of which have anti-inflammatory properties similar to those of parthenolide, may be worth investigating.
But Edzard Ernst, professor of Complementary Medicine at the University of Exeter, UK, is cautious. "We have reviewed the scientific literature for feverfew, and we have found that it has not had any clinical effects in fighting cancer. To extrapolate from [this laboratory work] is a leap of faith -- we need the clinical evidence."
Patel, N. M. et al. Paclitaxel sensitivity of breast cancer cells with constitutively active NF-κB is enhanced by IκBα super-repressor and parthenolide. Oncogene 19, 4159 - 4169 2000. | Article | PubMed | ISI | ChemPort |