Niclosamide, a drug used with tapeworm infections, attacks cells with a p53 deficiency causing apoptosis or cancer cell death and reducing tumour size by up to 50%; it can also restrict metastasis and cancer cell migration and inhibit cancer stem cells; while reducing chemo-resistance.
Niclosamide (or, Niclocide), is a teniacide in the anthelmintic family which is especially effective against cestodes (tapeworms). It has been approved for use in humans for nearly 50 years and is well-tolerated. Importantly, Niclosamide inhibits oxidative phosphorylation and stimulates adenosine triphosphatase activity in the mitochondria of the worms. This has been shown both in vitro and in vivo. This action plus the inhibitory effects of niclosamide on cancer stem cells make it a promising drug for cancer treatment (8).
It should be noted that this action against cancer is completely different to that of other antihelmintic compounds such as Mebendazole or Fenbendazole which both damage tubulin found in microtubules in worms and cancer cells.
1. Niclosamide attacks cancer cell mitochondria and combats p53 deficiency
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 lose power 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. It is estimated that an active p53 protein can regulate approximately 500 gene pathways in a cell. A
deficiency in protein 53 leads to 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, 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 (1) that Niclosamide reduced tumour growth by 50%.
Niclosamide literally uncouples the whole p53 mechanism.
2. Niclosamide blocks multiple signaling pathways of cancer stem cells
Several research groups have reported that Niclosamide also attacks multiple signaling pathways of cancer stem cells. In a recent study on oral squamous cell catcinoma (11), researchers showed that not only could Niclosamide block progression and migration of the cancer cells, it blocked stem cell development and even cisplatin based enrichment of the squamous cancer stem cells.
In 2012, researchers in one study (3) called for human clinical trials on the drug given the importance of their finding of its actions against cancer stem cells 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, Low Dose Naltrexone, and Melatonin with almost all cancers. Drugs like Niclosamide are particularly useful if there's chemo-resistance or a failure in p53, such as with CHEK2 message loss”
3. Niclosamide can overcome chemo resistance
In a 2023 study (6) with Osteosarcoma, niclosamide was shown to inhibit proliferation and migration, and induce apoptosis in both parental and chemo-resistant osteosarcoma cells, with much less toxicity in normal osteoblastic cells. The study showed that chemo-resistant cells were actually more sensitive than normal cancer cells.
4. Nicolsamide, 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. For example, in a 2021 trial with prostate cancer (
7), researchers state
"Niclosamide has preclinical activity against a wide range of cancers. In prostate cancer, it inhibits androgen receptor variant 7 and synergizes with abiraterone." The research is being conducted by the University of California, Davis.
This follows a 2015 paper (8) evaluating the potential of Niclosamide in treating cancer. This stated: "Niclosamide not only inhibits the Wnt/β -catenin, mTor, STAT3, NF-kB and Notch signaling 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."
In other studies it has also been shown to inhibit cancer cell migration and metastasis in colon cancer cells (2).
There is research where Niclosamide has been shown effective against platinum-resistant drugs for breast cancer (9)
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.
Warning: Niclosamide should not be used with Fenbendazole or Mebendazole.
Dose of Niclosamide
The Mayo Clinic talks of taking Niclosamide after a light meal for tapeworms at a level of up to 2 gm with adults. But for tapeworms, a single dose is usually enough although sometimes a week's course is recommended.
In the study (7) with Prostate cancer, Niclosamide was used with the drug Abiraterone at a level of 1200 mg three times a day. Diarrhoea was the most common side-effect.
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References
- Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers26 September; R Kumar et al;m Nat Commum; 2018 Sep 26;9(1):3931.
- 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
- Niclosamide is a potential candidate for the treatment of chemo-resistant osteosarcoma; Xiaoling Huang et al; Genet Mol Biol. 2023; 46(1): e20220136.
- Phase Ib trial of reformulated niclosamide with abiraterone/prednisone in men with castration-resistant prostate cancer; Mamta Parikh et al; Scientific Reports 18 March 2021; volume 11, Article number: 6377 (2021)
- Multi-targeted therapy of cancer by niclosamide: a new application for an old drug; Yonghe Li et al; Cancer Lett. 2014 Jul 10; 349(1): 8–14.
- Anthelminthic niclosamide inhibits tumor growth and invasion in cisplatin-resistant human epidermal growth factor receptor 2-positive breast cancer; Junjun Liu et al; Oncol Lett; 2021 Sep;22(3):666.
- How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? - Brandon J Aubrey 17 Nov 2017 Nature - https://www.nature.com/articles/cdd2017169
- The Antihelminthic Niclosamide Inhibits Cancer Stemness, Extracellular Matrix Remodeling, and Metastasis through Dysregulation of the Nuclear β-catenin/c-Myc axis in OSCC; Lin Hong-Wang et al; Scientific Reports volume 8, Article number: 12776 (Aug 24, 2018)
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