Niclosamide (B3)

Revitalizing a Tapeworm Drug: Niclosamide's Groundbreaking Role in Cancer Therapy

A versatile drug, long known for treating tapeworm infections, is making an impressive resurgence in the world of oncology. Niclosamide, first marketed under the trade name Niclocide, has exhibited powerful anticancer properties that could transform the way we approach cancer treatment.

Niclosamide is unique in its ability to selectively target cancer cells characterized by a p53 deficiency, a condition shared by most cancerous cells. This precision-based strike induces apoptosis, leading to cancer cell death and shrinkage of the tumor size by an impressive 50%. Beyond this, Niclosamide also exhibits an uncanny ability to restrain cancer cell migration and metastasis, while simultaneously inhibiting cancer stem cells.

Pioneer in Mitochondrial Combat

Mitochondria, often referred to as the powerhouse of the cell, are at the forefront of Niclosamide's ingenious attack strategy. A compromised cell, weakened by factors such as a faulty magnesium pump, excessive sodium, the effects of estradiol, and decreased oxygen levels, experiences mitochondrial shutdown and the turning off of the p53 gene. This gene, under normal conditions, governs controlled cell growth and division. Without its supervision, cells proliferate uncontrollably, culminating in cancer.

Niclosamide disrupts the energy production system of the mitochondria, causing a surge in the production of a fatty acid known as Arachidonic acid within the cancer cell. In cells where the p53 gene functions normally, this rise in Arachidonic acid is effectively managed through the activation of two genes, ALOx5 and ALOX 12B, which enhance cellular calcium levels. However, in p53-deficient cells, this protective mechanism fails, leading to an abundance of Arachidonic acid and subsequent cell death. This is the magic of Niclosamide—it selectively targets and eradicates cancer cells deficient in p53.

Groundbreaking research from Milan IFOM and Singapore Medical School, conducted both in vitro and in vivo, has demonstrated Niclosamide's potential. Mice injected with p53-deficient colon cancer cells showed a 50% reduction in tumor growth when treated with Niclosamide, solidifying its potential in cancer therapy.

A Powerhouse Against Cancer Stem Cells

Adding another feather to its cap, Niclosamide has shown prowess in blocking multiple signaling pathways of cancer stem cells—a feat unmatched by current chemotherapy drugs. Given the profound implications of this discovery, there have been strong calls for human clinical trials involving Niclosamide.

Safe and Effective

Niclosamide, in existence for over 50 years, is recognized by the World Health Organization as safe, cost-effective, and minimally harmful to healthy cells. This attribute lends itself well to its use in the field of cancer treatment.

Expanding Its Horizons

Encouraged by its therapeutic potential, the National Cancer Institute in the United States has endorsed clinical trials of Niclosamide against prostate and colorectal cancers. This follows a 2015 paper that praised Niclosamide for its abilities to inhibit various signaling pathways, target cancer cell mitochondria, induce cell cycle arrest, growth inhibition, and apoptosis, and impact cancer stem cells.

Niclosamide has shown promise in treating metastatic uveal (eye) melanoma and, when used in conjunction with Oxaliplatin, has demonstrated improved effectiveness and reduced neuropathy in colorectal cancer treatment.

As research continues to unfold, the tale of Niclosamide is a testament to the possibilities of drug repurposing, offering newfound hope in the ongoing battle against cancer.

References:

1. Nature; 26 September 2018: Mitochondrial uncoupling reveals a novel therapeutic opportunity for p53-defective cancers. https://www.nature.com/articles/s41467-%20018-05805-1
2. J Natl cancer Inst 2011; 103; 1018-1036: Novel Effect of niclosamide in metastatic progression of colon cancer by Sack U et al. https://pubmed.ncbi.nlm.nih.gov/21685359/
3. Chinese Journal of cancer 2012: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3777479/
4. https://www.thno.org/v07p1447.htm
5. https://mct.aacrjournals.org/content/16/2/300