cancer, HIV or AIDS, . The study was conducted on 18 rectal cancer patients at Memorial Sloan Kettering Cancer Center in Manhattan and had a 100 percent success rate, according to a paper published Sunday in the New . 15 Jan 2023 21:28:26 HSP27 is a molecular chaperone protein that is highly expressed in many cancers and associated with drug resistance and poor prognosis. The ePub format uses eBook readers, which have several "ease of reading" features Levy J.M.M., Towers C.G., Thorburn A. With the development of derivatives of the avermectin family that are more efficient and less toxic, relevant research on the anticancer mechanism of the derivatives still has great value. Ivermectin is a minor cytochrome P450 3A4 substrate and a p-glycoprotein substrate. Jan. 21, 2022 -- Doctors at Duke University are leading a national study to test whether three drugs could effectively treat COVID-19 including ivermectin . Zheng Z., Li G. Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer. Moreover, IVM was also found to have a good inhibitory effect on the prostate cancer cell line DU145 [51]. 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. The ePub format is best viewed in the iBooks reader. The present study represents the first study evaluating the anticancer efficacy of ivermectin in pancreatic cancer. Yan S., Ci X., Chen N., Chen C., Li X., Chu X., Li J., Deng X. Anti-inflammatory effects of ivermectin in mouse model of allergic asthma. Huang Z., Wu T., Liu A.Y., Ouyang G. Differentiation and transdifferentiation potentials of cancer stem cells. In a study that . Activated caspase-1 can cause pro-IL-1 and pro-IL-18 to mature and to be secreted. Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas. However, to date, no exact target for IVM action has been found. Cancer stem cells and radiotherapy: new insights into tumor radioresistance. This group explores and celebrates the successes of the repurposed drug Fenbendazole to help with cancer treatment. In another study, IVM inhibited the proliferation of U251 and C6 glioma cells by inhibiting the Akt/mTOR pathway [64]. (4) IVM can enhance the sensitivity of chemotherapeutic drugs and reduce the production of resistance. Ashour D.S. A small trial that saw 18 rectal cancer patients taking the same drug, dostarlimab, appears to have produced an astonishing result: The cancer vanished in every single participant . What this study does and does not show. Cancer stem cells and self-renewal. 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. I can't find ivermectin tablets anywhere. Autophagy is a lysosomal-dependent form of programmed cell death. The 5-year survival rate after diagnosis is approximately 47% [27,57]. Deepak K.G.K., Vempati R., Nagaraju G.P., Dasari V.R., N. S, Rao D.N., Malla R.R. It included data from Surgisphere, a company that also provided inaccurate patient data . PAKs in Human Cancer Progression: From Inception to Cancer Therapeutic to Future Oncobiology. Ivermectin induces apoptosis and autophagy is mutually regulated. Gallardo F., Mariam B., Gence R., Tilkin-Mariam A.-F. Macrocyclic lactones inhibit nasopharyngeal carcinoma cells proliferation through PAK1 inhibition and reduce in vivo tumor growth. In an experiment by Draganov, it was found that the release of lactate dehydrogenase (LDH) and activated caspase-1 was significantly increased in breast cancer cells after IVM intervention [37]. Diehn M., Clarke M.F. The study found that there was no difference in hospitalization rates between patients who received placebo and those who received ivermectin. A recent double-blind randomized study in Cali, Colombia found that ivermectin, used among adults with mild cases of COVID-19, "did not significantly improve the time to resolution of symptoms . Generating an ePub file may take a long time, please be patient. In gliomas, miR-21 can regulate the Ras/MAPK signaling pathway and enhance its effects on proliferation and invasion [65]. B. MM, E.-S. AA Therapeutic potential of myrrh and ivermectin against experimental Trichinella spiralis infection in mice. Hanafi H.A., Szumlas D.E., Fryauff D.J., El-Hossary S.S., Singer G.A., Osman S.G., Watany N., Furman B.D., Hoel D.F. 5. Yoshida G.J. Kumar R., Li D.Q. 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. In addition, PAK1 facilitates Wnt/-catenin signaling, make -catenin accumulate in the cytoplasm and translocate to the nucleus. natem | @natem | 1 day ago. Ivermectin can turn "cold" breast tumors "hot" We studied the effects of ivermectin in vivo using the 4T1 mouse model of TNBC. In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in . Ivermectin has powerful antitumor effects, including the inhibition of proliferation, metastasis, and angiogenic activity, in a variety of cancer cells. A new study evaluated the effect of ivermectin on time to recovery from coronavirus disease 2019 (COVID-19) in patients with mild to moderate disease. Overall, the specific environment of tumor cells will determine whether autophagy enhances or inhibits tumor development and improving autophagy activity has also become a new approach in cancer therapy. Wang J., Xu Y., Wan H., Hu J. Here's What You Need to Know about Ivermectin. For example, it was found in SK-MEL-28 melanoma cells that IVM can promote apoptosis as well as autophagy [74]. Nambaras study showed that IVM could significantly inhibit the proliferation of gastric cancer cells in vivo and in vitro and that the inhibitory effect of IVM depended on the expression of Yes-associated protein 1(YAP1)[39]. The incidence of breast cancer has increased each year, and it has become one of the female malignant tumors with the highest incidence in globally. RT @AFLDSorg: 'Ivermectin has anti-cancer properties.' @drCParks1 explains what the scientific research shows. Mechanisms of IVM-induced mitochondria-mediated apoptosis. "It is a far cry from an in vitro lab replication to helping humans," said Dr. Nasia Safdar, medical director of infection prevention at the University of Wisconsin-Madison Hospital. Effect of ivermectin on Trypanosoma brucei brucei in experimentally infected mice. Recently, ivermectin, a well-known anti-parasite drug, was reported to share the same mechanisms with them and have anti-tumor activity. Furthermore, Diaos study showed that IVM could inhibit the proliferation of the canine breast tumor cell lines CMT7364 and CIPp by blocking the cell cycle without increasing apoptosis, and the mechanism of IVM may be related to the inhibition of the Wnt pathway [33]. An experiment found that IVM could significantly enhance the inhibitory effects of erlotinib and cetuximab on lung cancer and colorectal cancer [50]. Zhang X., Qin T., Zhu Z., Hong F., Xu Y., Zhang X., Xu X., Ma A. Ivermectin Augments the In Vitro and In Vivo Efficacy of Cisplatin in Epithelial Ovarian Cancer by Suppressing Akt/mTOR Signaling. Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial. The decrease in the mitochondrial membrane potential and the cytochrome c is released from mitochondria into the cytoplasm was detected after the intervention of IVM in Hela cells [56].Therefore, we infer that IVM induces apoptosis mainly through the mitochondrial pathway. (Ub:Ubiquitination, P:Phosphorylation). Most of the anticancer research performed on the avermectin family has been focused on avermectin and IVM until now. Kim J.H., Choi H.S., Kim S.L., Lee D.S. Lespine A., Martin S., Dupuy J., Roulet A., Pineau T., Orlowski S., Alvinerie M. Interaction of macrocyclic lactones with P-glycoprotein: structure-affinity relationship. Top medical journals have rejected a paper about the study, and its main author, Flavio Cadegiani, an endocrinologist at the biotech company Applied Biology, has previously touted unproven COVID-19 medications, such as ivermectin, azithromycin, and antiworm compounds. Perspectives on the utility of moxidectin for the control of parasitic nematodes in the face of developing anthelmintic resistance. Subsequently, the inactivation Akt/mTOR signaling cannot inhibit the formation of the Beclin-1 complex, thus inducing the formation autophagosome. The functionality is limited to basic scrolling. Emerging Role of Circulating Tumor Cells in Gastric Cancer. An early study using cells in petri dishes suggested that ivermectin has antiviral properties at very high concentrations and could inhibit the pandemic coronavirus, SARS-CoV-2. 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. 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. Retweets. Han S.J., Lovaszi M., Kim M., DAgati V., Hasko G., Lee H.T. Dominguez-Gomez G., Chavez-Blanco A., Medina-Franco J.L., Saldivar-Gonzalez F., Flores-Torrontegui Y., Juarez M., Diaz-Chavez J., Gonzalez-Fierro A., Duenas-Gonzalez A. Ivermectin as an inhibitor of cancer stemlike cells. Prostate cancer is a malignant tumor derived from prostate epithelial cells, and its morbidity is second only to that of lung cancer among men in Western countries [49]. PAK1 allocates crosstalk between the PI3K and MAPK pathways. Liu Y., Fang S., Sun Q., Liu B. Anthelmintic drug ivermectin inhibits angiogenesis, growth and survival of glioblastoma through inducing mitochondrial dysfunction and oxidative stress. Kane N.S., Hirschberg B., Qian S., Hunt D., Thomas B., Brochu R., Ludmerer S.W., Zheng Y., Smith M., Arena J.P., Cohen C.J., Schmatz D., Warmke J., Cully D.F. Wang Y., Su J., Wang Y., Fu D., Ideozu J.E., Geng H., Cui Q., Wang C., Chen R., Yu Y., Niu Y., Yue D. The interaction of YBX1 with G3BP1 promotes renal cell carcinoma cell metastasis via YBX1/G3BP1-SPP1- NF-kappaB signaling axis. Recent studies have also found that IVM could promote the death of tumor cells by regulating the tumor microenvironment in breast cancer. We are experimenting with display styles that make it easier to read articles in PMC. As mentioned above, the broad-spectrum antiparasitic drug IVM, which is widely used in the field of parasitic control, has many advantages that suggest that it is worth developing as a potential new anticancer drug. Ivermectin is generally given with water on an empty stomach; however, administering ivermectin with food increases its bioavailability. Therefore, combination therapy is the most common method of chemotherapy. Therefore, IVM should be used in combination with other drugs to achieve the best effect, while the specific medication plan used to combine IVM with other drugs remains to be explored. Earlier, we mentioned the role of IVM in docetaxel-resistant prostate cancer [50] and gemcitabine-resistant cholangiocarcinoma [44]. Antoszczak M., Markowska A., Markowska J., Huczynski A. 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]. ). Ivermectin, a potential anticancer drug derived from an antiparasitic drug. Glioblastoma is the deadliest glioma, with a median survival time of only 14-17 months [61,62]. Ivermectin reverses the drug resistance in cancer cells through EGFR/ERK/Akt/NF-kappaB pathway. 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]. Biochemical and Biophysical Research Communications. Pancreatic cancer is an aggressive cancer characterized by high mortality and poor prognosis with survival of less than 5 years when advanced. In Jiang's experiment, IVM reversed the drug resistance of the vincristine-resistant colorectal cancer cell line HCT-8, doxorubicin-resistant breast cancer cell line MCF-7 and the chronic myelogenous leukemia cell line K562 [104]. Cervical cancer is one of the most common gynecological malignancies, resulting in approximately 530,000 new cases and 270,000 deaths worldwide each year. Not only does IVM not overlap with other therapies in term of its mechanism of action, but the fact that of IVM has multiple targets suggests that it is not easy to produce IVM resistance. Ivermectin is proven to treat a variety of different cancers. Dean M., Fojo T., Bates S. Tumour stem cells and drug resistance. 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 . Abstract. The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. 108K. Ivermectin is an anti-parasite medication used to treat a variety of parasitic diseases such as parasitic worms, hookworm and whipworm. ). Gastric cancer is one of the most common malignant tumors worldwide. Ivermectin: a potent new antiparasitic agent. IVM could inhibit the development of hepatocellular carcinoma by blocking YAP1 activity in spontaneous liver cancer Mob1b-/- mice [43].Cholangiocarcinoma is a malignant tumor that originates in the bile duct inside and outside the liver. It is characterized by double-layered or multilayered vacuolar structures containing cytoplasmic components, which are known as autophagosomes [77]. Overall, we speculate that IVM can regulate the Akt/mTOR, MAPK and other pathways that are essential for tumor cell proliferation by inhibiting PAK1 expression, which plays an anticancer role in most cancers. The study was done by . Likes. Nambara S., Masuda T., Nishio M., Kuramitsu S., Tobo T., Ogawa Y., Hu Q., Iguchi T., Kuroda Y., Ito S., Eguchi H., Sugimachi K., Saeki H., Oki E., Maehara Y., Suzuki A., Mimori K. Antitumor effects of the antiparasitic agent ivermectin via inhibition of Yes-associated protein 1 expression in gastric cancer. For some older drugs that are widely used for their original indications and have clinical data and safety information, drug repositioning allows them to be developed via a cheaper and faster cycle and to be used more effectively in clinical use clinically [29]. The river blindness drug Ivermectin and related macrocyclic lactones inhibit WNT-TCF pathway responses in human cancer. Hepatocellular carcinoma is the fourth leading cause of cancer death worldwide. The ACTIV-6 study enrolled 1,800 participants. As shown in Ivermectin is a specific inhibitor of importin alpha/beta-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. 1,553. This suggests that ivermectin may be an anticancer drug with great potential. 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. Intervention with IVM in the breast cancer cell lines MCF-7 and MDA-MB-231 significantly increased intracellular autophagic flux and the expression of key autophagy proteins such as LC3, Bclin1, Atg5, and the formation of autophagosomes can be observed [32]. P2X4 receptor exacerbates ischemic AKI and induces renal proximal tubular NLRP3 inflammasome signaling. Several studies have confirmed that IVM could reverse drug resistance by inhibiting P-gp and MDR-associated proteins [[101], [102], [103]]. Ivermectin neither reduced hospital admissions for worsening COVID-19 nor shortened the time that infected patients spent in the emergency room, according to data from a large randomized . Interestingly, IVM could also show activity against BRAF wild-type melanoma cells, and its combination with dapafinib could significantly increase antitumor activity. 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. Animal studies with rats given 3 times the maximum recommended human dose of 200 mcg/kg did not show any . This medicine is available only with your doctor's . Franklin K.M., Asatryan L., Jakowec M.W., Trudell J.R., Bell R.L., Davies D.L. In recent years, many studies have shown that autophagy is a double-edged sword in tumor development. A Colombian health worker . Ivermectin has been called a Covid "miracle" drug, championed by vaccine opponents, and recommended by health authorities in some countries. Didier A., Loor F. The abamectin derivative ivermectin is a potent p-glycoprotein inhibitor. Bao S., Wu Q., McLendon R.E., Hao Y., Shi Q., Hjelmeland A.B., Dewhirst M.W., Bigner D.D., Rich J.N. The study group included adult patients from 12 cities throughout Brazil, where ivermectin has been widely embraced and utilized since the early months of the pandemic. After treatment with IVM, the proliferation of multiple breast cancer cell lines including MCF-7, MDA-MB-231 and MCF-10 was significantly reduced. 5). We found that IVM inhibits tumor cell development in a PAK1-dependent manner in most cancers. Since the first report that IVM could reverse tumor multidrug resistance (MDR) in 1996 [22], a few relevant studies have emphasized the potential use of IVM as a new cancer. Kwak H.J., Kim Y.J., Chun K.R., Woo Y.M., Park S.J., Jeong J.A., Jo S.H., Kim T.H., Min H.S., Chae J.S., Choi E.J., Kim G., Shin S.H., Gwak H.S., Kim S.K., Hong E.K., Lee G.K., Choi K.H., Kim J.H., Yoo H., Park J.B., Lee S.H. An NIH trial may settle debate over ivermectin; officials warn people not to take animal formulation of the drug. Based on the studies suggesting efficacy in prophylaxis combined with the known safety profile of ivermectin, a citywide prevention program using ivermectin for COVID-19 was implemented in Itaja, a southern . Galluzzi L., Bravo-San Pedro J.M., Demaria S., Formenti S.C., Kroemer G. Activating autophagy to potentiate immunogenic chemotherapy and radiation therapy. p21-activated kinases in cancer. In addition, characteristic pyroptosis phenomena such as cell swelling and rupturing were observed. Interestingly, IVM also restored the sensitivity of the triple-negative breast cancer to the anti-estrogen drug tamoxifen [36], which also implies the potential for IVM to be used in endocrine therapy. Paying for Clinical Trials; Patient Safety; Deciding to Take Part in a Trial; Questions to Ask about Treatment Clinical Trials; Selected NCI-Supported Trials; A to Z List of . Drugs targeting BRAF mutations such as vemurafenib, dabrafenib and PD-1 monoclonal antibodies, including pembrolizumab and nivolumab have greatly improved the prognosis of melanoma [71,72]. Carneiro S.R., da Silva Lima A.A., de Fatima Silva Santos G., de Oliveira C.S.B., Almeida M.C.V., da Conceicao Nascimento Pinheiro M. Relationship between Oxidative Stress and Physical Activity in Women with Squamous Intraepithelial Lesions in a Cervical Cancer Control Program in the Brazilian Amazon. Find NCI-Supported Clinical Trials; What Are Clinical Trials? If you are pregnant, nursing, taking medication, or have a medical . Ivermectin, an antiparasitic drug, has been shown to possess anti-inflammation, anti-virus, and antitumor properties. 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. As the cost of the research and development of new anticancer drugs continues to increase, drug repositioning has become increasingly important. However, whether ivermectin affects CRC is still unclear. Abstract. 88]. treatment [[23], [24], [25], [26], [27]]. Old wine in new bottles: Drug repurposing in oncology. 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 . These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Campbell W.C., Fisher M.H., Stapley E.O., Albers-Schonberg G., Jacob T.A. Melotti A., Mas C., Kuciak M., Lorente-Trigos A., Borges I., Ruiz i Altaba A. The majority of cervical cancers are caused by human papillomavirus (HPV) infection [54,55]. A systematic literature review and network meta-analysis of effectiveness and safety outcomes in advanced melanoma. We believe that IVM can be further developed and introduced clinically as part of new cancer treatments in the near future. Only the paste. IVM halted the cell cycle in S phase and promoted apoptosis. Ivermectin is a macrolide antiparasitic drug with a 16-membered ring that is widely used for the treatment of many parasitic diseases such as river blindness, elephantiasis and scabies. Two studied the effects of intensive physical treatment plus selenium or placebo in preventing AIE's, and two studied the effects of Ivermectin, Diethylcarbamazine (DEC) (anti-filarial agents) and penicillin as prophylactic treatment for adeno lymphangitis(ADL) versus placebo.Both selenium trials reported no inflammatory episodes during the . Modulation of P2X4/P2X7/Pannexin-1 sensitivity to extracellular ATP via Ivermectin induces a non-apoptotic and inflammatory form of cancer cell death. Unfortunately, there have been no reports of clinical trials of IVM as an anticancer drug. 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 chemical structures of ivermectin and other avermectin family compounds in this review. Markowska A., Kaysiewicz J., Markowska J., Huczynski A. Doxycycline, salinomycin, monensin and ivermectin repositioned as cancer drugs. Liu J., Liang H., Chen C., Wang X., Qu F., Wang H., Yang K., Wang Q., Zhao N., Meng J., Gao A. Ivermectin induces autophagy-mediated cell death through the AKT/mTOR signaling pathway in glioma cells. Identifying the predominant or most important contributor to cell death in each cancer type and environment will be crucial in determining the effectiveness of IVM-based treatments. In addition, IVM shows potential for clinical application in asthma [20] and neurological diseases [21]. Ovarian cancer is a malignant cancer that lacks early clinical symptoms and has a poor therapeutic response. Nappi's experiment also proved that IVM combined with erlotinib to achieved a synergistic killing effect by regulating EGFR activity and in HCC827 lung cancer cells [50]. Current Advances in the Treatment of BRAF-Mutant Melanoma. Gallardo F., Teiti I., Rochaix P., Demilly E., Jullien D., Mariam B., Tilkin-Mariam A.-F. Macrocyclic Lactones Block Melanoma Growth, Metastases Development and Potentiate Activity of Anti BRAF V600 Inhibitors. It is highly effective against many microorganisms including some viruses. Interestingly, ivermectin can also inhibit tumor stem cells and reverse multidrug resistance and exerts the optimal effect when used in combination with other chemotherapy drugs. The discoverers of IVM, Japanese scientist Satoshi mura and Irish scientist William C. Campbell, won the Nobel Prize in Physiology or Medicine in 2015 [7,8]. Lim S.M., Syn N.L., Cho B.C., Soo R.A. Acquired resistance to EGFR targeted therapy in non-small cell lung cancer: Mechanisms and therapeutic strategies. Existing research is sufficient to demonstrate the great potential of IVM and its prospects as a novel promising anticancer drug after additional research. Apoptosis is a programmed cell death that is regulated by genes to maintain cell stability. 36. Summary of IVM promotes programmed cell death. Gewirtz D.A. Hence several favorable signals were detected in a study with several structural biases against ivermectin. The excessive activation of PAK1 is involved in the formation, development, and invasion of various cancers [ I take small doses of 6-12 mg regularly (3-4 x/week) after reading about it at NIH.gov, which someone else has now posted. 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]. Ivermectin is used to treat river blindness (onchocerciasis), intestinal infection from threadworms (strongyloidiasis), and other kinds of worm infections. Patel H., Yacoub N., Mishra R., White A., Long Y., Alanazi S., Garrett J.T. Mechanisms of IVM-induced P2 4/P2 7/NLRP3-mediated pyroptosis. Further studies showed that IVM could inhibit CSCs by regulating the PAK1-STAT3 axis [96]. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. ATP binding transport family-mediated drug efflux and overexpression of P-glycoprotein (P-gp) are widely considered to be the main causes of tumor MDR [[98], [99], [100]]. Views. In this study, we sought to explore whether ivermectin (IVM), a macrolide antiparasitic agent, could overcome the resistance of cancer cells to the therapeutic drugs. Medicinal chemistry strategies to discover P-glycoprotein inhibitors: An update. IVM promotes degradation of PAK1 by ubiquitination/proteasome pathway, thereby inhibiting the Akt/mTOR signaling pathway. Ivermectin is an anthelmintic. Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. Geyer J., Gavrilova O., Petzinger E. Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice. Finally, activated PARP and caspase-3 trigger apoptosis. Deng F., Xu Q., Long J., Xie H. Suppressing ROSTFE3dependent autophagy enhances ivermectininduced apoptosis in human melanoma cells. IVM could block the cell cycle and induce cell apoptosis through a KPNB1-dependent mechanism in ovarian cancer [59]. After intervention with IVM, the cell cycle of HeLa cells was blocked at the G1/S phase, and the cells showed typical morphological changes related to apoptosis. 2 Ivermectin: From theory to clinical application. And to many, the claims simply seem implausible. Mingyang Tang, Xiaodong Hu, [], and Qiang Fang. Targeting Heat Shock Protein 27 in Cancer: A Druggable Target for Cancer Treatment? Gasdermin D(GSDMD)is a substrate for activated caspase-1 and is considered to be a key protein in the execution of pyroptosis [86,87]. Effects of ivermectin on blood-feeding Phlebotomus papatasi, and the promastigote stage of Leishmania major. We found that the anticancer . 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. Molinaro A.M., Taylor J.W., Wiencke J.K., Wrensch M.R. Moreover, the expression of the homeobox protein NANOG, octamer-binding protein 4 (OCT-4) and SRY-box 2 (SOX-2), which are closely related to the self-renewal and differentiation ability of stem cells in CSCs, were also significantly inhibited by IVM. Ivermectin has been touted as a treatment or prevention method for COVID-19 . Its morbidity has increased by an average of 2% annually worldwide and the clinical treatment effect is not satisfactory [[45], [46], [47]]. It . The FDA-approved drug . Anti-Inflammation, anti-virus, and angiogenic activity, in a PAK1-dependent manner in most cancers, J.K.... 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