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New Study: How Ivermectin Kills Prostate Cancer Cells
I was doing the background research for my lecture on Prostate Cancer in my IPAK-EDU Course, The Biology of Cancer, looking for treatments that enhance genomic instability - and Guess What?
I spent the first semester of my course, The Biology of Cancer, reviewing all of the aspects of The Hallmarks of Cancer. This morning, firing up Pubmed to continue preparing my lecture prostate cancer, I found this gem of a study, which happens to be a collaboration between my former employer, The University of Pittsburgh, and Southern Medical University-Guangzhou. I don’t know the authors:
Title: Integrated analysis reveals FOXA1 and Ku70/Ku80 as targets of ivermectin in prostate cancer
The authors exposed various prostate cancer cells lines to Ivermectin and found that ivermectin binds to two proteins: FOXA1 and Ku70/Ku80. This leads to the inhibition of androgen receptor (AR), E2F1 expression, and DNA damage repair activity. The cells stopped dividing (G0/G1 cell cycle arrest), experience extensive DNA damage, and die.
A retrospective study of the rates of cancer and rates of death from cancer among unvaccinated people who prophylactically used Ivermectin over a long period of time vs those who did not is in order.
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 in tumor cells, few studies have focused on the exact target of ivermectin. Herein, we report the pharmacological effects and targets of ivermectin in prostate cancer. Ivermectin caused G0/G1 cell cycle arrest, induced cell apoptosis and DNA damage, and decreased androgen receptor (AR) signaling in prostate cancer cells. Further in vivo analysis showed ivermectin could suppress 22RV1 xenograft progression. Using integrated omics profiling, including RNA-seq and thermal proteome profiling, the forkhead box protein A1 (FOXA1) and non-homologous end joining (NHEJ) repair executer Ku70/Ku80 were strongly suggested as direct targets of ivermectin in prostate cancer. The interaction of ivermectin and FOXA1 reduced the chromatin accessibility of AR signaling and the G0/G1 cell cycle regulator E2F1, leading to cell proliferation inhibition. The interaction of ivermectin and Ku70/Ku80 impaired the NHEJ repair ability. Cooperating with the downregulation of homologous recombination repair ability after AR signaling inhibition, ivermectin increased intracellular DNA double-strand breaks and finally triggered cell death. Our findings demonstrate the anticancer effect of ivermectin in prostate cancer, indicating that its use may be a new therapeutic approach for prostate cancer.
Citation: Lv S, Wu Z, Luo M, Zhang Y, Zhang J, Pascal LE, Wang Z, Wei Q. Integrated analysis reveals FOXA1 and Ku70/Ku80 as targets of ivermectin in prostate cancer. Cell Death Dis. 2022 Sep 1;13(9):754. doi: 10.1038/s41419-022-05182-0. PMID: 36050295; PMCID: PMC9436997.
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