Table of Contents

The Anticancer Potential of Ivermectin: Mechanisms of Action and Therapeutic Implications

Narges Lotfalizadeh1,Arian Gharib2,Ashkan Hajjafari3,Hassan Borji4, andZeynab Bayat5,*

1Department of Clinical Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran

2Department of Clinical Sciences, Faculty of Veterinary Medicine, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran

3Department of Pathobiology, Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran

4Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran 5Department of Biology, Faculty of Sciences, Shahid Bahonar University ofKerman, Kerman, Iran

Abstract:

Ivermectin is a well-known antiparasitic drug inthe macrolide class with a 16-membered ring. Its use in treatingvarious parasitic diseases, including onchocerciasis, lymphatic filariasis, and strongyloidiasis, is well established. The present study aimed to review the mechanisms of action and therapeutic implicationsof Ivermectin as an anticancer agent.Recently, the potential use of ivermectin in cancer treatment has emerged. A growing body of evidence suggests that ivermectin has anticancer properties, makingit an attractive candidate for treatingvarious types of cancer.Studies have shown that ivermectin targets multiple signaling pathways, including the Wnt/β-catenin, PI3K/Akt/mTOR, and STAT3 pathways, to inhibit cancer cell proliferation and induce apoptosis. Inhibition of these pathways by ivermectin leads to suppressionof cancer cell growth, making it an effective antitumor agent. Additionally, ivermectin has been shown to induce autophagy, which can lead to programmed cell death in cancer cells.One of the significant advantages of ivermectin as an anticancer drug is its safety profile. It has been usedfor over three decades, and its safety has been well-established in humans. Furthermore, it is easily available and affordable, making it a promising alternative to conventional chemotherapy.Several preclinical studies have demonstrated the efficacy of ivermectin against various types of cancer, including breast, lung, and colon cancer. However, further research is needed to evaluate its clinical effectivenessin humans. Clinical trials are underway to investigate ivermectin’s safety and efficacy in cancer treatment.In conclusion, usingivermectin as an anticancer drug is a promising area of research. Its ability to target multiple signaling pathways and induce programmed cell death in cancer cells makes it an attractive candidate for the treatment of various types of cancer. Itssafety profile and low cost make it a feasible alternative to conventional chemotherapy.

1. Introduction:

Ivermectin(IVM), a broad-spectrum antiparasitic drug, has been used for several decades to treatvariousparasitic diseases1. Its effectiveness is due to its ability to activate glutamate-gated chloride channels, which results in excessive chloride influx and hyperpolarization of neurons, leading to somatic muscle paralysis and the eventual death of the parasites. Ivermectin iseffective against several parasitic diseases, including scabies, elephantiasis, river blindness, trypanosomiasis, trichinosis, malaria, leishmaniasis,and schistosomiasis2.In addition to its antiparasitic properties, IVMhas shown potential as an antiviral agent3. It has been found to inhibit the replication of flaviviruses by blocking the NS3 helicase activity and interfering with the transport of viral proteins to the nucleus via the α/β-mediated mechanism3. Ivermectin also displays antiviral activity against viruses such as dengue and HIV-14. Recent studies haveshown that IVMmay also be effective against SARS-CoV-2, whichcaused the COVID-19 pandemic5.

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