I was doing some general purpose digging into anti-viral agents (where I eneded up ordering another jug of ivermectin) and then looked on the bookcase shelf. There was an almost empty tube of Fenbendazole worming paste. This one was intended for horses. I’d originally gotten it some years back as I was franticly trying to find a cure for head tilt in my rabbits. ( I did, it worked ). Why did I do that? Because the Vet was not encouraging and most folks took the path of “rabbits are cheap just get another one”. Treatment was not clear or easily available.
So, OK, after that I kept a tube of it around for deworming and any recurance of head tilt in a bunny. But now the bunnies are gone. Yet I’d not tossed it out.
I got to wondering about the active ingredient Fenbendazole. It, like Ivermectin (the other half of my bunny cure) has some broad activities. Mosty used to get rid of worms, but it does other things too.
Fenbendazole is a broad spectrum benzimidazole anthelmintic used against gastrointestinal parasites including: giardia, roundworms, hookworms, whipworms, the tapeworm genus Taenia (but not effective against Dipylidium caninum, a common dog tapeworm), pinworms, aelurostrongylus, paragonimiasis, strongyles, and strongyloides that can be administered to sheep, cattle, horses, fish, dogs, cats, rabbits, and seals.
Drug interactions may occur if salicylanilides such as dibromsalan and niclosamide are co-administered. Abortions in cattle and death in sheep have been reported after using these medications together. Abortions in domestic ruminants have been associated with concurrent use of anti-trematode therapeutic agents.
Despite being widely used as a dewormer in many species, toxicity has been reported. Birds (storks, pink pelicans, vultures, pigeons and doves) and reptiles (vipers, turtles and tortoises) have shown toxicity associated with bone marrow suppression, intestinal crypt cell necrosis, and distal villi sloughing.
Fenbendazole is poorly absorbed from the gastrointestinal tract in most species. The LD50 in laboratory animals exceeds 10 g/kg when administered orally.
So you can get a good dose on the worms in the gut without too much being absorbed into the body. This is an apple flavored paste for horses. Rubbed on skin it does slowly soak in, but that’s not the intended mode. The biggest issues for non-worming uses is just getting it into the body.
So, OK, imagine my surprise when it turned up on a search for anti-virals and as used by some folks to treat cancers (and leading to the speculation that maybe more cancers are caused by viruses than originally thought…)
We describe antitumor activities of vitamin E succinate (VES), an anti-oxidant and fenbendazole (FBZ), a commonly used veterinary anthelmintic. We used VES and FBZ, at low concentrations, singly and in combination, to test their inhibitory effects on proliferation of human and mouse prostate cancer cells in vitro. Administered alone, FBZ inhibited proliferation faster than VES in both mouse and human prostate cancer cell lines and a synergistic effect between both was also observed. Apoptosis was the likely mechanism for the observed effect. These drugs may deserve to be tested for their efficacy in the control of prostate cancer using in vivo models.
In recent years, there has been a great deal of interest in proteasome inhibitors as a novel class of anticancer drugs. We report that fenbendazole (FZ) (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate) exhibits a potent growth-inhibitory activity against cancer cell lines but not normal cells. We show here, using fluorogenic substrates, that FZ treatment leads to the inhibition of proteasomal activity in the cells. Succinyl-Leu-Leu-Val-Tyr-methylcoumarinamide (MCA), benzyloxycarbonyl-Leu-Leu-Glu-7-amido-4-MCA, and t-butoxycarbonyl-Gln-Ala-Arg-7-amido-4-MCA fluorescent derivatives were used to assess chymotrypsin-like, post-glutamyl peptidyl-hydrolyzing, and trypsin-like protease activities, respectively. Non-small cell lung cancer cells transiently transfected with an expression plasmid encoding pd1EGFP and treated with FZ showed an accumulation of the green fluorescent protein in the cells due to an increase in its half-life. A number of apoptosis regulatory proteins that are normally degraded by the ubiquitin-proteasome pathway like cyclins, p53, and IκBα were found to be accumulated in FZ-treated cells. In addition, FZ induced distinct ER stress-associated genes like GRP78, GADD153, ATF3, IRE1α, and NOXA in these cells. Thus, treatment of human NSCLC cells with fenbendazole induced endoplasmic reticulum stress, reactive oxygen species production, decreased mitochondrial membrane potential, and cytochrome c release that eventually led to cancer cell death. This is the first report to demonstrate the inhibition of proteasome function and induction of endoplasmic reticulum stress/reactive oxygen species-dependent apoptosis in human lung cancer cell lines by fenbendazole, which may represent a new class of anticancer agents showing selective toxicity against cancer cells.
Keywords: Anticancer Drug, Apoptosis, Cell Growth, ER Stress, p53, Proteasome, Reactive Oxygen Species (ROS)
Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways
Nilambra Dogra, Ashok Kumar & Tapas Mukhopadhyay
Scientific Reports volume 8, Article number: 11926 (2018) Cite this article
Drugs that are already clinically approved or experimentally tested for conditions other than cancer, but are found to possess previously unrecognized cytotoxicity towards malignant cells, may serve as fitting anti-cancer candidates. Methyl N-(6-phenylsulfanyl-1H benzimidazol-2-yl) carbamate [Fenbendazole, FZ], a benzimidazole compound, is a safe and inexpensive anthelmintic drug possessing an efficient anti-proliferative activity. In our earlier work, we reported a potent growth-inhibitory activity of FZ caused partially by impairment of proteasomal function. Here, we show that FZ demonstrates moderate affinity for mammalian tubulin and exerts cytotoxicity to human cancer cells at micromolar concentrations. Simultaneously, it caused mitochondrial translocation of p53 and effectively inhibited glucose uptake, expression of GLUT transporters as well as hexokinase (HK II) – a key glycolytic enzyme that most cancer cells thrive on. It blocked the growth of human xenografts in nu/nu mice model when mice were fed with the drug orally. The results, in conjunction with our earlier data, suggest that FZ is a new microtubule interfering agent that displays anti-neoplastic activity and may be evaluated as a potential therapeutic agent because of its effect on multiple cellular pathways leading to effective elimination of cancer cells.
As a consequence of this, there’s a bunch of men with protate cancer that are using it as something of a last hope. Some with the help of their M.D. and some on their own.
I also ran into discussion of it for killing off warts. It halted the human papilloma virus. So having a scrap of it left over, and having a dozen or so tiny warts about the size of the head of a pin on the tops of my feet and backs of my knees (where the skin is thinest and scratching more likely), I smeared it on for about 3 days (then I ran out). Just a thin film one or 2 times a day. That was a couple of weeks ago.
Inspection of my feet and the backs of the knees (hello mirror…) showed the tiny warts are gone. They had been there, slowly increasing in number, for about 30 years. Now it’s just skin.
So yeah, on my next run to the Pet Store getting another tube of fenbendazole is on the cards. It’s always nice to have a dewormer on hand, but one that stops warts, kills viruses, and in a pinch whacks on cancer cells? Now that’s special!
Here’s an interesting page listing all sorts of other drugs that can have uses off-lable as an anti-cancer agent. It’s a fascinating list.
Here’s a sample out of the middle of the list. Why? Because some of these were a big surprise to me.
* Doxycycline – breast cancer, prostate cancer; converts cancer stem cells to mere mortals in conjunction with berberine or IVC; however it has its problems. See here
* Melatonin – Some oncologists refer to it as ‘The sleeping drug’. But it reduces natural oestrogen, is anti-inflammatory and has at least 5 different ways of attacking cancer cells. It is almost universally effective. See Here
* Naltrexone – as Low Dose Naltrexone (LDN) and used with vitamin D and alpha lipoic acid, has almost universal ability to boost the immune system and provide some pain relief. Increasingly used with cannabis at night and CBD by day.
Then there are at least another 10 drugs with a number of research studies on specific cancers, for example,
* Accutane – GBM, neuroblastoma, breast cancer (with metformin) and can correct cancer stem cells. (But accutane has strong side-effects)
* Celebrex – prostate, lung, breast, colorectal, brain cancer
* Cimetidine – colorectal cancer, gastric cancer, melanoma, kidney cancer; Independent review on Cimetidine and cancer HERE
* Dipyridamole – melanoma, colorectal, breast, TNBC (works well with the anti-histamine cimetidine)
* Fenbendazole – GBM, NSCLC, lymphoma, metastatic Colorectal Cancer, prostate cancer (also blocks uptake of sugar).
* Itraconozole – pancreatic, NHL, endometrial, NSCLC, prostate, breast cancer and TNBC
* Ivermectin – Lymphoma, leukemia, and solid tumours such as ovarian, TNBC and breast cancer.
So it looks like there are lots of potential drugs, many available OTC, that can be used for slowing, stopping, or curing virus infections and cancers (many caused by viruses).
In particular, Fenbendazol did a dandy job on some very small warts. I need a new tube so I can try it on a wart on the sole of my foot where the skin is a whole lot thicker and that lack of absorption issue may show up. Sure, I could just go get it frozen… but where’s the fun in that?
I don’t know that I’ll ever need to explore the potential use against cancer. Let’s hope not. OTOH, nice to know about “for that day”.
There are related compounds in the same family that have shown promise on other cancers. In particular brain cancer. So this looks like a very fruitful area of drug development.