Integrated analysis reveals FOXA1 and Ku70/Ku80 as direct targets of ivermectin in prostate cancer
Shidong Lv, Zeyu Wu, Mayao Luo, Yifan Zhang, Jianqiang Zhang, Laura E Pascal, Zhou Wang, Qiang Wei
bioRxiv, 2022
Ivermectin is a widely used antiparasitic drug and shows promising anticancer activity in various cancer types. Although multiple signaling pathways modulated by ivermectin have been identified, few studies have focused on the exact target of ivermectin. Herein, we report the pharmacological effects and direct targets of ivermectin in prostate cancer (PCa). Ivermectin caused G0/G1 arrest, induced cell apoptosis, DNA damage, and decreased androgen receptor (AR) signaling in PCa cells. Using integrated omics profiling, including RNA-seq and thermal proteome profiling, we found that the forkhead box protein A1 (FOXA1) and non-homologous end joining (NHEJ) repair executer Ku70/Ku80 were the direct targets of ivermectin. The binding of ivermectin and FOXA1 reduced the chromatin accessibility of AR and the G0/G1 cell cycle regulator E2F1, leading to cell proliferation inhibition. The binding of ivermectin and Ku70/Ku80 impaired the NHEJ repair ability. Cooperating with the downregulation of homologous recombination repair after AR inhibition, ivermectin triggered synthetic lethality. Our findings demonstrate the anticancer effect of ivermectin in prostate cancer, indicating that its use may be a new therapeutic approach for PCa.
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Graham49
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I've used it for PCa since Nov 2020, but I was on Lupron long before that and still am, so hard to claim anything since I've been stable all the way through.
My poison (Taxotere) was administered under a Dr.'s care. Approved for its use after years of the highest medical science scrutiny and trials on humans. I don't know I guess the internet and its false argument that conspiracies keep worm killer from being administered are more important to you. I suppose you haven't even told your Dr. you are using it?
You failed to mention the hed is 1/10th that of mice, in other words one would have to take about 10x the recommended dose that killed these pca’s, so highly unlikely to od or have any side effects
Dont understand all the pathways, etc but I like this quote: "22RV1 xenograft model was used to determine effect of ivermectin on CRPC progression in vivo. Male mice bearing 22RV1 xenografts were castrated when tumors exceeded 300 mm3 135 and 136 randomized to vehicle or Ivermectin administered 10 mg/kg 3 times per week. Ivermectin137 significantly reduced 22RV1 tumor volume growth (Fig. 2F), lowering Ki-67 and PSA levels, 138 and increasing the γH2A.X level in tumor tissue (Fig. 2G).139
140 Taken together, these results revealed that ivermectin could inhibit prostate cancer progression in
141 vitro and in vivo by inducing G0/G1 arrest, apoptosis, and DNA damage.
However, 10mg/kg? For me at 210 lbs (95.45kg) that would be does of 950mg! Can a human even take that much? My Covid prophylaxis does is 0.2 mg/kg and if you get it, bump up to 0.6 mg/kg. But 10?
Thanks, that helps, but even at .81 mg/kg, each dose is 77mg and I think that was given 3x day. Looks like LD(50) is 50mg/kg where normal therapeutic dose is 0.2 mg/kg. So 4x normal therapeutic dose 3x day. Why does that scare me? Since this is generic at this time, I doubt we see human studies. Not sure what to do with this info but put it in the fun to know catagory.
No it’s77mg 3x/Wk and the human lethal dose Is 500mg/kg human equivalent code (hed) read it more carefully, def doable n well tolerated In some human trials
Your weight… you can choose how many days on and off. Many people do 3 days on , 4 days off. It has a cumulative effect. Many take it every day, at this point, how much more do we all have to loose??
The human equivalent dose (hed) Is about 1mg/kg which is about 1/10th that of mice, which is well tolerated in human trials. Ivermectin was discovered 50 years ago n won a Nobel peace award by discovery and is used to treat parasites 🦠 now have found can block the androgen receptor signals in pca not to mention causes apoptosis. They are looking at it as a redirecting agent in killing n blocking p cancer ♋️ cells…
BB_1, Are you taking 12 mg or 12 mcg? The dosage details are very vague at this point. I was recommended 20 mg per day, but my doctor wants to drop it to 20 mcg. Any side effects? Thanks.
Not yet tracking PSA. Still have to do my biopsy next month. The way I look it Ivermectin will not hurt me , it may help fight prostate cancer plus I will never get worms!
you def need to take more than 12 mcg. I took 48 mg/2 days for a total of 6 doses in 12 days. I’ve been on zytiga n orgavix for 7 months n just did 7 weeks of radiation ☢️ n .43 was lowest I could get my psa. After taking the ivermectin for2 Wk’s it dropped to.11, number I couldn’t attain after 7 months of adt alone. I’m getting off the adt now n waiting for testosterone to return to get the true tale as last month when I got off adt my psa rose to over 6. I’ll recheck in two weeks when test returns n give update…
It’s readily available now that Covid is pretty much under control as people were using it with pretty good results from the studies I’ve read, contrary to what they were trying to make people believe as it’s relatively cheap to make. Merck makes it under the name strombectol and can get it online from reputable Indian pharmacies. Also had a friend get it from Mexico n claims the quality is good but would do research on it from there. All day chemist from India is where I got mine w the remarkable results thus far…
oh man I hope not, did you get a tracking number and or do they have a 1-800#, anyway all day chemist seems to b legit as they follow up every two or three days w updates… gl
My attitude as well. I have pitavastatin (Livalo)in my back pocket if this doesn't work. My cholesterol is slightly elevated, so it too won't hurt. Hope all goes well.
“IVM administered 10 mg/kg orally 3 times per week. IVM significantly reduced tumor volume and serum PSA levels after castration, delaying time to CRPC (Figure 4F). Moreover, IVM significantly reduced full-length AR (AR-FL) and AR-V7 protein expression and 22RV1 tumor volume growth in vivo.”
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Cancer and stress: not directly related to prostate cancer but interesting research
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