Ivermectin and Cancer
by David Archibald
29 September 2021
Ivermectin reached fame as a cure for internal parasites, yet more fame for saving countries such as India from the scourge of the Covid virus, and will likely take its place in cancer treatment. As a paper devoted to ivermectin’s potential in cancer treatment states:
Ivermectin, an antiparasitic compound of wide use in veterinary and human medicine, is clearly a strong candidate for repositioning, based on the fact that:
- It is very safe, causing almost no side-effects other than those caused by the immune and inflammatory responses against the parasite in infected patients, and
- It has proven antitumor activity in preclinical studies.
The first thing to consider is the pharmacokinetics, which is how much will be absorbed into the body and how long it will stay there before it is excreted. The following table suggests that dosing to at least 2 mg/kg of body weight is safe:
That produces a serum concentration of ivermection of about 0.25 µg/ml. Ivermectin has a half-life of 12 hours. Another test of ivermectin’s safety found that subcutaneous ivermectin (0.2 mg/kg, once a day) produced serum ivermectin levels between 11.4 and 17.2 ng/ml with no significant accumulation over 16 days.
Ivermectin has at least three pathways in suppressing cancer. Firstly, as shown in a test on breast cancer cell lines, ivermectin inactivates the protein kinase PAK1 and blocks the PAK1-dependent growth of human ovarian cancer and NF2 tumor cell lines. PAK proteins encoded by the PAK1 gene are critical for cytoskeleton reorganization and nuclear signalling.
PAK1 is essential for the growth of more than 70% of all human cancers, including breast, prostate, pancreatic, colon, gastric, lung, cervical and thyroid cancers, as well as hepatoma, glioma, melanoma, multiple myeloma, and for neurofibromatosis tumours. The inhibition of PAK1 decreases the phosphorylation level of Akt, resulting in the blockade of the Akt/mTOR signaling pathway and thereby activating autophagy in breast cancer cells.
Secondly, ivermectin was found to induce chloride-dependent membrane hyperpolarization and cell death in leukemia cells. That paper also found that Ivermectin synergizes with chemo agents cytarabine and daunorubicin to induce cell death in leukaemia cells.
Thirdly, ivermectin inhibits the expression of WNT-TCF targets, mimicking dnTCF. Its low concentration effects are rescued by direct activation by TCF. It represses the levels of C-terminal β-CATENIN phosphoforms and of CYCLIN D1 in an okadaic acid-sensitive manner, indicating its action involves protein phosphatases. In vivo, ivermectin selectively inhibits TCF-dependent, but not TCF-independent, xenograft growth without obvious side effects.
Ivermectin is also synergistic with chemotherapy, and reverses resistance in chemo-refractory cancers. For example in the colon cancer cell line HCT-8, ivermectin at 2.6 µg/ml triples the efficacy of the chemotherapy drug vincristine from an IC 50 0.08 µg/ml to 0.02 µg/ml. For chemo-refractory HCT, ivermectin at 2.6 µg/ml increases vincristine’s efficacy by 31.1 fold from an IC 50 0.88 µg/ml to 0.03 µg/ml. In the following graphic, mice were treated with ivermectin (2 mg/kg) and/or VCR (0.2 mg/kg) by intraperitoneal injection daily for 27 days:
Similar effects are seen with other chemotherapy drugs, such as doxorubicin and adriamycin. Ivermectin has been shown to also be a chemosensitiser in oesophageal cancer cell lines, as per the following diagram:
KYSE150 and KYS30 are oesophageal cancer cell lines. The figure above shows that ivermectin at 2.2 µg/ml by itself has little effect. The chemotherapy drugs 5-FU at 26 µg/ml kills about 25% of both cancer cell lines. But the combination of ivermectin and 5-FU raises that to about 70%.
Discussion
Ivermectin is very cheap and very safe. Everyone on chemotherapy or radiotherapy should consider supplementing their regimen with it.
It is also likely to enhance the effect of molecules that activate the apoptotic cascade of the caspases such as resveratrol, berberine, quercetin, boswellia and Silymarin.
David Archibald is the author of The Anticancer Garden in Australia
