A common anti-parasitic drug known as Ivermectin was recently found to have anti-cancer properties. Is it effective? What does the research say? Let’s explore.
What is Ivermectin Used For?
Ivermectin is commonly used as an anti-parasitic drug used to treat strongyloidiasis and onchocerciasis. These infections occur due to parasitic worms in the body. Ivermectin can also be applied topically to treat parasitic skin conditions such as rosacea and to eliminate parasites such as head lice. It was also used commonly for animal health in the early 1980s as well.
How can it Help Against Cancer?
Various trials have been held over the course of a few years that have significant promise in ivermectin inhibiting the growth of cancer. The good news mainly has been the broad-spectrum working of Ivermectin. It has proven to be fairly effective against a large variety of cancers. The types of cancers it worked against included ovarian cancer, breast cancer, Oesophageal Squamous Cell Carcinoma, and many others.
One research that aimed to demonstrate the effectiveness of ivermectin against ovarian cancer treated normal ovarian cells IOSE8o and the ovarian cancer cells TOV-21 and SKOV3. The treatment was continued for 24 hours. Flow cytometry took place to demonstrate the apoptosis and changes to the normal cell cycle as well. Ivermectin was also used to treat A278o and TOV-21G after they were allowed to grow to 90% confluency and a 10 microlitre pipette was used to make a wound. The percentage of wound healing over time was measured.
The experiment determined that Ivermectin successfully inhibited the normal ovarian cell cycle as well as the proliferation of ovarian cancer cells. Even with a dose of 2000 micrograms/kg, no CNS toxicity was exhibited.
Research has also shown the effectiveness of combination therapy with ivermectin and immune checkpoint blockade therapy against breast cancer. Checkpoint blockade therapy works by blocking checkpoint proteins and preventing them from binding with their complementary proteins, which ensues a T-cell response to start killing cancer cells.
Checkpoint blockade therapy only works on “hot” tumors, which are tumors that have already been infiltrated by T-cells. Cold tumors, in contrast, are those which have little to no T-cell infiltration. This is where Ivermectin plays its part and helps to convert cold tumors to hot tumors. The research was performed on mice where a protein, HMGB1, which is a hallmark of immunogenic cell death, was observed. Tumors from the mice which were treated with ivermectin were shown to be lacking HMGB1 which showed that Ivermectin did induce an immunogenic response in the cancer cells.
Esophageal Squamous Cell Carcinoma is another type of cancer on which ivermectin can possibly be effective. In yet another study, Ivermectin was shown successfully to suppress the growth of esophageal squamous cell carcinoma by inducing apoptosis. This effectiveness was demonstrated both, in vitro and in vivo. Furthermore, ivermectin also prevented tumors from exhibiting invasion and metastasis in mice. The drug was also shown to increase the sensitivity of esophageal squamous cell carcinoma to cisplatin or 5-fluorouracil. The study effectively determined that Ivermectin showed significant promise as a therapeutic drug for esophageal squamous cell carcinoma.
In addition to this, Ivermectin has also been verified as being useful in inducing apoptosis in chronic myeloid leukemia. It can do this without being disruptive to normal hematopoietic cells which only furthers its effectiveness as a cancer therapy drug.
There are a large number of other cancers that ivermectin is highly useful for, including cancers of the digestive system, cancers in the urinary tract, hematological cancers other than CML, cancers in the reproductive system, brain glioma, melanoma, and lung cancers.
All the trials and researches mentioned have shown that Ivermectin is effective against a vast variety of tumors and has multiple effects.
What is the Mechanism of Ivermectin Acting Against Cancer?
Ivermectin’s mechanism of action is not limited to a single effect, in fact, the reason why it is possibly effective as a cancer therapy is that it has multiple, powerful, anti-tumor effects. These include inhibition of the cell proliferation, prevention of invasion and metastasis, inducing apoptosis, and, as we saw with checkpoint blockade therapy, it can also induce an immune response when needed
Mechanically speaking, ivermectin can inhibit the P-glycoprotein pump. This pump induces a multidrug phenotype in cancer cells. Additionally, it can also act as an ionophore and manipulate the regulation of chloride channels which can generate apoptosis and even osmotic cell death in many cases.
Another interesting mechanism of ivermectin includes diminishing the function of Mitochondrial Complex I, which prevents electron motion during oxidative phosphorylation, which is the pathway that generates ATP for each cell.
Ivermectin can also induce immunogenic cell death with the help of HMGB1 and ATP by promoting inflammation. Another interesting aspect of ivermectin is that it increases a cell’s sensitivity to ATP as well which can bring about an ATP-induced immune response that destroys the cell. Ivermectin can also help in inducing autophagy by triggering a sequence of events that comes about when it stimulates the expression of Beclin1 and Atg5. The drug promotes the poly-ubiquitination of a kinase known as PAK1 which helps in degradation in the proteasome which can then inhibit the Akt/mTOR pathway.
There are other mechanisms still being determined by research and trials which make ivermectin the useful anti-tumor drug it is on its way to becoming.
What Does This Mean for Cancer Therapy?
Ivermectin is just one of many drugs that have surfaced in recent years that show promise against malignant tumors. There is a high possibility that ivermectin will be used in chemotherapy commonly in the near future, however, we must understand that tumor cells can easily develop drug resistance and render the effects of many drugs useless. Even so, the use of ivermectin with other drugs in conjunction with therapy can be highly effective for a vast number of malignant tumors.
Despite this, the development of drugs that can counter this resistance and be more aggressive with anti-cancer activity is an urgent matter that needs to be addressed with as many resources and scientific manpower as possible. We are in the hopes that scientists can boost the effectiveness of ivermectin up in a way that when it is introduced for chemotherapy, it is highly effective and possibly revolutionary.
Conclusion
Ivermectin has been effective and highly useful as an antiparasitic drug for decades now. However, its usefulness as an anti-cancer drug has just surfaced. There has been immense research that shows ivermectin’s usefulness as a chemotherapy drug. Ivermectin makes use of multiple mechanisms to inhibit cancer growth and it can also be used in combination therapy with many other drugs. We are hoping that it will be introduced as an anti-cancer drug soon and when it does there are ways to counter drug resistance as well.
Dr. Paul Zhang at the Institute of Integrative BioOncology in Houston provides evidence-based treatments for a wide range of cancers. Call today for more information.
References
1 Zhan X, Li N. The Anti-Cancer Effects of Anti-Parasite Drug Ivermectin in Ovarian Cancer. InOvarian Cancer-Updates in Tumour Biology and Therapeutics 2021 Jan 13. IntechOpen.
2 Draganov D, Han Z, Rana A, Bennett N, Irvine DJ, Lee PP. Ivermectin converts cold tumors hot and synergizes with immune checkpoint blockade for the treatment of breast cancer. NPJ Breast Cancer. 2021 Mar 2;7(1):1-1.
3 Chen L, Bi S, Wei Q, Zhao Z, Wang C, Xie S. Ivermectin suppresses tumor growth and metastasis through degradation of PAK1 in oesophageal squamous cell carcinoma. Journal of cellular and molecular medicine. 2020 May;24(9):5387-401.
4 Wang J, Xu Y, Wan H, Hu J. Antibiotic ivermectin selectively induces apoptosis in chronic myeloid leukemia through inducing mitochondrial dysfunction and oxidative stress. Biochemical and biophysical research communications. 2018 Feb 26;497(1):241-7.
5 Tang M, Hu X, Wang Y, Yao X, Zhang W, Yu C, Cheng F, Li J, Fang Q. Ivermectin, a potential anticancer drug derived from an antiparasitic drug. Pharmacological Research. 2020 Sep 21:105207.
