A longitudinal study was undertaken in three hyperendemic foci in Mali and Senegal with 15 to 17 years of annual or six-monthly ivermectin treatment in order to assess residual levels of infection . (1) Although a large number of research results indicate that IVM affects multiple signaling pathways in tumor cells and inhibits proliferation, IVM may cause antitumor activity in tumor cells through specific targets. Epigenetic therapy for ovarian cancer: promise and progress. Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas. The Panel reviewed other clinical studies of IVM for the treatment of COVID-19. Kibria G., Hatakeyama H., Harashima H. Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system. IVM regulates the tumor microenvironment and mediates immunogenic cell death, which may be a new direction for research exploring anticancer mechanisms in the future. It works by interfering with the nerve and muscle functions of worms, by paralyzing and killing them. Last. P2X4 receptors (P2X4Rs) represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders. The study found that patients with Covid-19 treated in hospital who "received ivermectin early reported substantial recovery" and that there was "a substantial improvement and reduction in . ). IVM could inhibit the DDX23/miR-12 signaling pathway by affecting the activity of DDX23 helicase, thereby inhibiting malignant biological behaviors. OBrien C.A., Kreso A., Jamieson C.H. Intuyod K., Hahnvajanawong C., Pinlaor P., Pinlaor S. Anti-parasitic Drug Ivermectin Exhibits Potent Anticancer Activity Against Gemcitabine-resistant Cholangiocarcinoma In Vitro. When they compared the excluded ivermectin group of 75 to the remaining 198 subjects in the placebo groups, ivermectin reduced SP 9.3% vs. 21.2%. When the external environment is suitable, CSCs will rapidly proliferate to reactivate the formation and growth of tumors. IVM not only has strong effects on parasites but also has potential antiviral effects. 5). In recent years, many studies have shown that autophagy is a double-edged sword in tumor development. On Aug. 23, a judge issued an emergency order to the hospital to begin administering 30 milligrams of ivermectin a day to the patient, as prescribed by a Front Line COVID-19 Critical Care Alliance . PAKs in Human Cancer Progression: From Inception to Cancer Therapeutic to Future Oncobiology. Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. But the result of . After intervention with IVM, the expression of caspase-3 in DLD1 and Ls174 T cells increased, indicating that IVM has an apoptosis-inducing effect and inhibits the expression of the downstream genes AXIN2, LGR5, and ASCL2 in the Wnt/-catenin pathway. Thanh Huong P., Gurshaney S., Thanh Binh N., Gia Pham A., Hoang Nguyen H., Thanh Nguyen X., Pham-The H., Tran P.T., Truong Vu K., Xuan Duong N., Pelucchi C., La Vecchia C., Boffetta P., Nguyen H.D., Luu H.N. Here's What You Need to Know about Ivermectin. It was based on a very small flawed 2002 study mentioned in a 2011 study. After using the autophagy inhibitor bafilomycin A1 or siRNA to downregulate Beclin1, IVM-induced apoptosis was significantly enhanced, which suggested that enhanced autophagy will reduce IVM-induced apoptosis and that IVM-induced autophagy can protect tumor cells from apoptosis. P2X4 receptor exacerbates ischemic AKI and induces renal proximal tubular NLRP3 inflammasome signaling. Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death. Methods We used two solid tumor cell lines (HCT-8 colorectal cancer cells and MCF-7 . Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-kappaB pathway. In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in . In Nappi's experiment, it was found that IVM could enhance the drug activity of the anti-androgen drug enzalutamide in the prostate cancer cell line LNCaP and reverse the resistance of the prostate cancer cell line PC3 to docetaxel [50]. The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. However, after using the autophagy inhibitors chloroquine and wortmannin or knocking down Bclin1 and Atg5 by siRNA to inhibit autophagy, the anticancer activity of IVM significantly decreased. 64,74]. The relationship between apoptosis and autophagy is very complicated, and the cross talk between the two plays a vital role in the development of cancer [82]. Arcangeli S., Pinzi V., Arcangeli G. Epidemiology of prostate cancer and treatment remarks. In a study by Hashimoto, it found that IVM inhibited the proliferation of various ovarian cancer cell lines, and the mechanism was related to the inhibition of PAK1 kinase [58]. Mechanisms of IVM-induced mitochondria-mediated apoptosis. already built in. Geyer J., Gavrilova O., Petzinger E. Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. Wang J., Xu Y., Wan H., Hu J. Ivermectin(IVM) is a macrolide antiparasitic drug with a 16-membered ring derived from avermectin that is composed of 80% 22,23-dihydroavermectin-B1a and 20% 22,23-dihydroavermectin-B1b [1]. A few weeks ago, William C. Campbell and Satoshi Omura, the scientists who developed ivermectin, won a Nobel Prize for the research that led to development of the drug, which has vastly reduced . Renal cell carcinoma is a fatal malignant tumor of the urinary system derived from renal tubular epithelial cells. An experiment found that IVM could significantly enhance the inhibitory effects of erlotinib and cetuximab on lung cancer and colorectal cancer [50]. Diana A., Carlino F., Franzese E., Oikonomidou O., Criscitiello C., De Vita F., Ciardiello F., Orditura M. Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes. Melanoma is the most common malignant skin tumor with a high mortality rate. The ePub format uses eBook readers, which have several "ease of reading" features In another study, IVM inhibited the proliferation of U251 and C6 glioma cells by inhibiting the Akt/mTOR pathway [64]. Choi S.K., Kam H., Kim K.Y., Park S.I., Lee Y.S. Therefore, in future research, it is necessary to continue to explore the specific mechanism of IVM involved in regulating the tumor microenvironment, angiogenesis and EMT. Recent studies have also pointed out that it has a promising inhibitory effect on the SARS-CoV-2 virus, which has caused a global outbreak in 2020 [19]. This may be related to the regulation of multiple signaling pathways by ivermectin through PAK1 kinase. Previous studies have indicated that PAK1 is located at the intersection of multiple signaling pathways related to tumorigenesis and is a key regulator of cancer signaling networks (Fig. Hence several favorable signals were detected in a study with several structural biases against ivermectin. Drug repositioning is a shortcut to accelerate the development of anticancer drugs. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. Triple-negative breast cancer (TNBC) refers to cancer that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2(HER2) and is the most aggressive subtype of breast cancer with the worst prognosis. Furthermore, according to a report by Zhang, IVM can enhance the efficacy of cisplatin to improve the treatment of epithelial ovarian cancer, and the mechanism is related to the inhibition of the Akt/mTOR pathway [60]. In mid-2020, an ivermectin study published in the prestigious New England Journal of Medicine was retracted. This group explores and celebrates the successes of the repurposed drug Fenbendazole to help with cancer treatment. The article, "Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen," is a review of various studies on the antiviral effects of ivermectin. Chen Y.P., Chan A.T.C., Le Q.T., Blanchard P., Sun Y., Ma J. Nasopharyngeal carcinoma. Markowska A., Kaysiewicz J., Markowska J., Huczynski A. Doxycycline, salinomycin, monensin and ivermectin repositioned as cancer drugs. Mastrangelo E., Pezzullo M., De Burghgraeve T., Kaptein S., Pastorino B., Dallmeier K., de Lamballerie X., Neyts J., Hanson A.M., Frick D.N., Bolognesi M., Milani M. Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug. In healthy volunteers, the dose was increased to 2 mg/Kg, and no serious adverse reactions were found, while tests in animals such as mice, rats, and rabbits found that the median lethal dose (LD50) of IVM was 10-50 mg/Kg [112] In addition, IVM has also been proven to show good permeability in tumor tissues [50]. "The drug induces a response in certain patients, and several trial patients stayed on selinexor for more than 12 months, including one for over 42 months," adds Dr. Lassman, who also is associate director for clinical trials at the Herbert Irving Comprehensive Cancer Center. Hashimoto H., Messerli S.M., Sudo T., Maruta H. Ivermectin inactivates the kinase PAK1 and blocks the PAK1-dependent growth of human ovarian cancer and NF2 tumor cell lines. We found that IVM inhibits tumor cell development in a PAK1-dependent manner in most cancers. The reason for the proclamation was the rise in the number Didier A., Loor F. The abamectin derivative ivermectin is a potent p-glycoprotein inhibitor. It can be triggered by two activation pathways: the endogenous endoplasmic reticulum stress/mitochondrial pathway and the exogenous death receptor pathway [75,76]. HSP27 is a molecular chaperone protein that is highly expressed in many cancers and associated with drug resistance and poor prognosis. Autophagy is a lysosomal-dependent form of programmed cell death. Kobayashi Y., Banno K., Kunitomi H., Tominaga E., Aoki D. Current state and outlook for drug repositioning anticipated in the field of ovarian cancer. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Existing research is sufficient to demonstrate the great potential of IVM and its prospects as a novel promising anticancer drug after additional research. Computational searching of DrugBank, a database of approved drugs, was performed using the principles of twodimensional similarity . Patel H., Yacoub N., Mishra R., White A., Long Y., Alanazi S., Garrett J.T. This work was supported by the Science Research Innovation Team Project of Anhui Colleges and Universities (2016-40), the Bengbu City Natural Science Foundation (2019-12), the Key Projects of Science Research of Bengbu Medical College (BYKY2019009ZD) and National University Students Innovation and Entrepreneurship Training Program (201910367001). Fritz L.C., Wang C.C., Gorio A. Avermectin B1a irreversibly blocks postsynaptic potentials at the lobster neuromuscular junction by reducing muscle membrane resistance. Earlier, we mentioned the role of IVM in docetaxel-resistant prostate cancer [50] and gemcitabine-resistant cholangiocarcinoma [44]. Goudie A.C., Evans N.A., Gration K.A., Bishop B.F., Gibson S.P., Holdom K.S., Kaye B., Wicks S.R., Lewis D., Weatherley A.J. natem | @natem | 1 day ago. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. What this study does and does not show. On the other hand, ivermectin promotes programmed cancer cell death, including apoptosis, autophagy and pyroptosis. Types of Cancer Treatment; Side Effects of Cancer Treatment; Clinical Trials Information. IVM could significantly reduce the mitochondrial membrane potential and inhibit mitochondrial respiration and ATP production. We are experimenting with display styles that make it easier to read articles in PMC. Ravegnini G., Sammarini G., Nannini M., Pantaleo M.A., Biasco G., Hrelia P., Angelini S. Gastrointestinal stromal tumors (GIST): Facing cell death between autophagy and apoptosis. Han S.J., Lovaszi M., Kim M., DAgati V., Hasko G., Lee H.T. Wurth R., Thellung S., Bajetto A., Mazzanti M., Florio T., Barbieri F. Drug-repositioning opportunities for cancer therapy: novel molecular targets for known compounds. In addition, there is also no clinically applicable therapeutic drug currently [34,35]. The Prime Minister of Malaysia proclaimed a state of Emergency Ordinance on the 12th January 2021. This was related to the induction of mitochondrial dysfunction and oxidative stress. Tumor microenvironment: Challenges and opportunities in targeting metastasis of triple negative breast cancer. PRR can identify pathogen-associated molecular patterns (PAMPs) that are structurally stable and evolutionarily conserved on the surface of pathogenic microorganisms and damage-associated molecular patterns (DAMPs) produced by damaged cells [84,85]. The DDX23 helicase activity affects the expression of miR-12 [66]. . the display of certain parts of an article in other eReaders. 15 Jan 2023 21:28:26 Nasopharyngeal carcinoma is a malignant tumor derived from epithelial cells of the nasopharyngeal mucosa. Views. Ivermectin is an anti-parasite medication used to treat a variety of parasitic diseases such as parasitic worms, hookworm and whipworm. Targeting autophagy in cancer. The inflammasome is a multimolecular complex containing pattern recognition receptor (PRR), apoptosis-associated speck-like protein containing a CARD (ASC), and pro-caspase-1. Ivermectin has been used off-label widely since the original in vitro study by Caly et al. Nishio found that IVM could significantly inhibit the proliferation of H1299 lung cancer cells by inhibiting YAP1 activity [43]. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. Antibiotic ivermectin selectively induces apoptosis in chronic myeloid leukemia through inducing mitochondrial dysfunction and oxidative stress. Dou Q., Chen H.N., Wang K., Yuan K., Lei Y., Li K., Lan J., Chen Y., Huang Z., Xie N., Zhang L., Xiang R., Nice E.C., Wei Y., Huang C. Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. Second, IVM seems to induce mixed cell death in tumor cells, which is also a controversial issue. Therefore, this review summarized the latest findings on the anticancer effect of IVM and discussed the mechanism of the inhibition of tumor proliferation and the way that IVM induces tumor programmed cell death to provide a theoretical basis for the use of IVM as a potential anticancer drug. Summary of IVM promotes programmed cell death. However, whether ivermectin affects CRC is still unclear. DEAD-box RNA helicase DDX23 modulates glioma malignancy via elevating miR-21 biogenesis. 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