Niclosamide, a drug used to deal with tapeworm infections, attacks cells with a p53 deficiency, a deficiency that the majority of cancer cells possess, causing apoptosis or cancer cell death and reducing tumour size by up to 50%; it can also attack restrict metastasis and cancer cell migration and inhibit cancer stem cells.
1. Niclosamide attacks cancer cell mitochondria
As cells are progressively weakened through, for example, a failure of the magnesium pump on their surface and thus too much sodium entering the cell, the influence of oestradiol and lowered oxygen levels, the cells' mitochondria power down and the p53 gene switches off. Under normal circumstances, p53 is in charge of a regulated cell growth and division. Without p53 in charge, the cells go out of control, growing rapidly. This is cancer.
Niclosamide (trade name Niclocide) interferes with the energy production system of the mitochondria and causes significant increases in the production of a fatty acid called Arachidonic acid in the cancer cell.
If the p53 gene is operating properly, it switches on two genes (ALOx5 and ALOX 12B) which increase calcium in the cell and deal with the excess of Arachidonic acid.
But in p53-deficient cells, this defence system is unavailable and the excess of Arachidonic acid cause the death of the cell. So, Niclosamide specifically targets cancer cells with a p53 deficiency.
Having worked this all out in test tubes, the researchers (from Milan IFOM and Singapore Medical School) took mice and injected them with p53-deficient colon cancer cells. After these took hold the researchers showed that Niclosamide reduced tumour growth by 50%.
In other studies it has also been shown to inhibit cancer cell migration and metastasis in colon cancer cells (2).
2. Niclosamide blocks multiple signaling pathways of cancer stem cells
Several research groups have reported that Niclosamide also attacks multiple signalling pathways of cancer stem cells. Researchers (3) called for human clinical trials on the drug given the importance of this finding and that there are no chemotherapy drugs in existence capable of dealing with cancer stem cells. This review shows that it has important effects reported both in vitro and in animals.
It has minimal effects with healthy cells. Niclosamide has been around for more than 50 years and is deemed a safe, cheap and effective drug by the WHO.
Chris Woollams, former Oxford University Biochemist and a founder of CANCERactive said, ”There are several repurposed, old drugs we believe have merit in the fight against cancer; for example, we like anti-histamines, Loratadine and Cimetidine, LDN and Melatonin with almost all cancers.”
3. Nicolsamide and prostate cancer, colorectal cancer
The National Cancer Institute in America is now supporting
Clinical Trials using Niclosamide as an agent against prostate cancer and colorectal cancer.
This follows a
2015 paper evaluating the potential of Niclosamide in treating cancer. This stated: "Niclosamide not only inhibits the Wnt/
β -catenin, mTor, STAT3, NF-kB and Notch signalling pathways, but also targets mitochondria in cancer cells to induce cell cycle arrest, growth inhibition and apoptosis. Moreover, the inhibitory effects of niclosamide on cancer stem cells provide further evidence for its consideration as a promising drug for cancer therapy."
There is also research (4) with uveal (eye) melanoma which had metastasised to the liver, and Niclosamide.
Finally there is research (5) using Niclosamide alongside Oxaliplatin for colorectal cancer, where Niclosamide reduced neuropathy and increased effectiveness of the drug.
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References
- Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers. Nature; 26 September 2018
- Sack U et al. Novel Effect of niclosamide in metastatic progression of colon cancer J Natl cancer Inst 2011; 103; 1018-1036
- Chinese Journal of cancer 2012: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777479/
- https://www.thno.org/v07p1447.htm
- https://mct.aacrjournals.org/content/16/2/300