Parthenolide, a sesquiterpene lactone and the principle bioactive ingredient of the herb feverfew, has been shown on multiple occasions to attack cancer stem cells largely through the nuclear factor kappa-B pathway. Parthenolide is also found in magnolia and can also be used to treat migraine.
What is Feverfew?
Feverfew, or wild chamomile, or Bachelor’s button, (tanacetum parthenium), is a truly powerful herb because of several bioactive ingredients called sesquiterpene lactones including one in particular, Parthenolide, found in the largest concentration in the flowers and the fruit. (Updated several times from an article dating back to 2007, by Chris Woollams)
Feverfew is actually a member of the chrysanthemum family and, although native originally to the Balkan peninsular, the plant is now widely cultivated across the globe.
It has multiple pharmacologic properties, for example: anti-inflammatory, anticancer, cardiotonic, suppression of muscle spasms, stimulating menstrual flow and as an enema for worms (1).
Traditional uses of Feverfew
Since Ancient Greek and Egyptian times, Feverfew has been used to treat a variety of illnesses – from rheumatoid arthritis, insect bites, stomach ache and toothache to period pain, fever and migraines.
Feverfew is still commonly used for migraines - guidelines from both the American Academy of Neurology and the American Headache Society based on research evidence suggest that a feverfew extract may be effective and should be considered for migraine prevention. That extract is Parthenolide.
In research, Parthenolide reduces smooth muscle spasms and the constriction of blood vessels in the brain. One 4-month study (2) showed feverfew reduced migraines by 40%. And a 2011 randomised, controlled trial showed a combination of sub-lingual Feverfew and ginger could provide migraine relief in two hours in 63% of patients (3). Feverfew crosses the blood-brain-barrier.
Feverfew and cancer stem cells - the research
Parthenolide doesn’t just attack cancer cells; it attacks cancer stem cells. And, when no orthodox cancer drug currently seems capable of this, the finding is particularly important. So much so, that the FDA promised to 'fast track' the development and use of feverfew in 2005. We are still waiting.
Pancreatic cancer - Pancreatic cancer contains a large number of different types of cancer stem cells at its heart. In 2005 there were a number of studies using parthemolide.. In one (4), parthenolide and a non-steroidal anti-inflammatory, sulindac, synergistically brought about growth suppression and inhibited the nuclear factor-kappa B pathway in pancreatic carcinoma cells.
In 2010, ‘in vitro’ research showed that parthenolide could inhibit pancreatic cancer cells’ proliferation and cause apoptosis (7).
Multiple Myeloma - As long ago as 2003, Johns Hopkins Medical School found a particular type of cancer stem cell in the bone marrow microenvironment which was both the origin of MM and the driver of recurrence. Research studies showed that parthenolide had a positive effect on the bone marrow microenvironment and a 'multi-faceted effect against MM cells, causing apoptosis. This appears to be enhanced by the drug dexamethasone. The activity against MM cells appears to involve reactive oxygen species and involve catalase. Unfortunately, different MM populations have different levels of catalase (11).
Breast cancer - Researchers from Indiana Medical School were looking at what might tackle NF- kappa B, which is known to promote pancreatic cancer cell migration; their research had previous shown that NF-kappa B caused cancer cell migration in breast cancer too.
Dr Nakshratri of Indiana showed that a daily intake of Parthenolide could suppress metastases ‘in vivo’ in mice with breast cancer and could increase the response to Paclitaxel (taxol).
By 2013 other Sesquiterpene lactones, such as costunolide, were being studied alongside parthenolide. Both were shown to selectively decrease detyrosinated tubulin in cancer cells independent of their inhibition of NF-κB.The two compounds showed reduction in the frequency of microtentacles and inhibition of reattachment in breast cancer. Better still, parthenolide and costunolide can decrease detyrosinated microtubules without significantly disrupting the overall microtubule network or cell viability. Thus they selectively attack cancer cells, whereas researchers showed Paclitaxel and colchicine were indiscriminate in their disruption of the microtubule network (9).
Leukaemia - Also in 2005, a team of researchers including Monica Guzman, PhD, of the University of Rochester Medical School, showed that Parthenolide was a potent anti-leukaemia aid and could kill cancer stem cells, without damaging healthy cells. It was also compared in the studies to the drug Cytarabine, commonly used at that time for leukaemia. The parthenolide gave significantly better results. This is what prompted the FDA to ‘fast track’ the herb and ingredient. A 2021 study (12) from the Medical School of Chiang Mai in Thailand, showed that costunolide and parthenolide, both from Magnolia sirindhorniae inhibited leukemic cell proliferation.
Cancer stem cells are not killed by any chemotherapy drugs, and live to fight another day, helping the tumour to grow again. For this reason they are sometimes called ‘Initiating Cells’.
In 2013 an ‘in vivo’ study in animals infected with child leukemia (ALL) took place. The parthenolide killed the Leukaemia-Initiating cells.
Prostate cancer – By 2009, researchers (7) at the National Cancer Institute were showing that Parthenolide could attack cancer stem cells in prostate cancer. (Prostate cancer, is second to Pancreatic cancer in terms of numbers of different cancer stem cells found in tumours.)
Go to: Top ten natural compounds that attack cancer stem cells
Lung cancer - in 2018 a study showed that parthenolide could inhibit the tumour-promoting effects of nicotine in lung cancer. It could inhibit VEGF expression (a common factor in NSCLC) and induce apoptosis. Both parthenolide and costunolide are also found in the shrub Magnolia sirindhorniae. Honokiol also comes from the magnolia bush (the best Honokiol supplements contain magnol) and is also known to have these anti-cancer and anti-proliferative effects in many cancers including lung cancer.
Go to: Honokiol has anti-tumour effects; restricts growth and metastasis
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References
- Feverfew: Systematic review; Anil Pareek et al; Pharmacognosy; 2011.
- Deiner et al; 2005;
- Headache; 2011; Roger K Cady et al.
- Michele T Yip-Schneider et al;
- Web MD;
- Paraskevi Diamanti et al; Bristol University Molecular Sciences, UK
- Brian T Kawasaki et al; Prostate. 2009 Jun 1;69(8): 827–837.
- Jun-Wei Liu et al; J Exp Clin Canc Res; 2010
- 2013; Breast Cancer Research, Rebecca A Whipple et al;
- 2018; Wamidh H Talib; Biomed Pharmacother
- Parthenolide-induced apoptosis in multiple myeloma cells; Wei Wang et al; Apoptosis; 2006 Dec;11(12):2225-35
- .Costunolide and parthenolide from Champi Sirindhorn (Magnolia sirindhorniae) inhibit leukemic cell proliferation in K562 and molt-4 cell lines; .Sawalee Saosathan et al; Nat Prod Res; 2021 Mar;35(6):988-992.