It was also proven that IVM has a synergistic effect with cytarabine and daunorubicin on the treatment of leukemia. In short, the relationship between IVM-induced apoptosis and autophagy involves a complex regulatory mechanism, and the specific molecular mechanism needs further study. 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]. The four faces of autophagy: implications for cancer therapy. (4) IVM can enhance the sensitivity of chemotherapeutic drugs and reduce the production of resistance. MDR of tumor cells is the main cause of relapses and deaths after chemotherapy [97]. The Prime Minister of Malaysia proclaimed a state of Emergency Ordinance on the 12th January 2021. Earlier, we mentioned the role of IVM in docetaxel-resistant prostate cancer [50] and gemcitabine-resistant cholangiocarcinoma [44]. Molinaro A.M., Taylor J.W., Wiencke J.K., Wrensch M.R. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The phenomenon of IVM-induced autophagy has also been reported in glioma and melanoma [ 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. It . Dong Z., Yu C., Rezhiya K., Gulijiahan A., Wang X. Downregulation of miR-146a promotes tumorigenesis of cervical cancer stem cells via VEGF/CDC42/PAK1 signaling pathway. ASC, Apoptosis-associated speck-like protein containing a CARD; ALCAR, acetyl-L-carnitine; CSCs, Cancer stem cells; DAMP, Damage-associated molecular pattern; EGFR, Epidermal growth factor receptor; EBV, Epstein-Barr virus; EMT, Epithelial mesenchymal-transition; GABA, Gamma-aminobutyric acid; GSDMD, Gasdermin D; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HER2, Human epidermal growth factor receptor 2; HMGB1, High mobility group box-1 protein; HSP27, Heat shock protein 27; LD50, median lethal dose; LDH, Lactate dehydrogenase; IVM, Ivermectin; MDR, Multidrug resistance; NAC, N-acetyl-L-cysteine; OCT-4, Octamer-binding protein 4; PAK1, P-21-activated kinases 1; PAMP, Pathogen-associated molecular pattern; PARP, poly (ADP- ribose) polymerase; P-gp, P-glycoprotein; PRR, pattern recognition receptor; ROS, Reactive oxygen species; STAT3, Signal transducer and activator of transcription 3; SID, SIN3-interaction domain; siRNA, small interfering RNA; SOX-2, SRY-box 2; TNBC, Triple-negative breast cancer; YAP1, Yes-associated protein 1, ivermectin(PubChem CID6321424), avermectin(PubChem CID6434889), selamectin(PubChem CID9578507), doramectin(PubChem CID9832750), moxidectin(PubChem CID9832912). Campbell W.C., Fisher M.H., Stapley E.O., Albers-Schonberg G., Jacob T.A. Therefore, combination therapy is the most common method of chemotherapy. This medicine is available only with your doctor's . Quote Tweets. RAS activation directly initiates PAK1, MAPK and PI3K/Akt pathway. The objective of this study was to evaluate the influence of ivermectin on CRC using CRC cell lines SW480 and SW1116. Recent studies have found that IVM could be used as an inhibitor of HSP27 phosphorylation to enhance the activity of anti-EGFR drugs in EGFR/HER2- driven tumors. Draganov D., Gopalakrishna-Pillai S., Chen Y.R., Zuckerman N., Moeller S., Wang C., Ann D., Lee P.P. This study to examine ivermectin, as well as a few other current medications to gauge their effectiveness against COVID-19, goes by the name of ACTIV-6. In a study using mouse models of pancreatic cancer, the researchers found that in fact, PD-L1 is not highly expressed on pancreatic cancer cells. 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. Types of Cancer Treatment; Side Effects of Cancer Treatment; Clinical Trials Information. Satoshi mura and William C. Campbell won the 2015 Nobel Prize in Physiology or Medicine for the discovery of the excellent efficacy of ivermectin against parasitic diseases. The functionality is limited to basic scrolling. 5). We believe that IVM can be further developed and introduced clinically as part of new cancer treatments in the near future. P2X4 receptors (P2X4Rs) represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders. Ivermectin has powerful antitumor effects, including the inhibition of proliferation, metastasis, and angiogenic activity, in a variety of cancer cells. 672. HSP27 is a molecular chaperone protein that is highly expressed in many cancers and associated with drug resistance and poor prognosis. Moreover, IVM was also found to have a good inhibitory effect on the prostate cancer cell line DU145 [51]. IVM.YAP1 plays an oncogenic role in tumorigenesis, indicating the possibility of the use of IVM as a YAP1 inhibitor for cancer treatment . As a member of the PAK family of serine/threonine kinases, PAK1 has a multitude of biological functions such as regulating cell proliferation and apoptosis, cell movement, cytoskeletal dynamics and transformation [108]. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment. 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 . Deng found that IVM could activate the nuclear translocation of TFE3 and induce autophagy-dependent cell death by dephosphorylation of TFE3 (Ser321) in SK-MEL-28 melanoma cells [74]. Ivermectin has been touted as a treatment or prevention method for COVID-19 . Didier A., Loor F. The abamectin derivative ivermectin is a potent p-glycoprotein inhibitor. 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. The clinical trials described in this table are RCTs that had the greatest impact on the Panel's recommendation. It's reportedly a very good, but simple and inexpensive drug. Ivermectin is used to treat river blindness (onchocerciasis), intestinal infection from threadworms (strongyloidiasis), and other kinds of worm infections. 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. "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. Avermectin family drugs such as selamectin [36,41,113], and doramectin [114] also have anticancer effects, as previously reported. IVM halted the cell cycle in S phase and promoted apoptosis. RT @AFLDSorg: 'Ivermectin has anti-cancer properties.' @drCParks1 explains what the scientific research shows. In a study published in the journal Oncotarget on July 6, Gregory Riggins, M.D., Ph.D., professor of neurosurgery and oncology at the Johns Hopkins University School of Medicine, and his team used two different mouse models to determine that the anti-parasitic drug mebendazole could slow or stop the growth and spread of both early and late-stage pancreatic cancer. Kwon Y.J., Petrie K., Leibovitch B.A., Zeng L., Mezei M., Howell L., Gil V., Christova R., Bansal N., Yang S., Sharma R., Ariztia E.V., Frankum J., Brough R., Sbirkov Y., Ashworth A., Lord C.J., Zelent A., Farias E., Zhou M.M., Waxman S. Selective Inhibition of SIN3 Corepressor with Avermectins as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer. Kim J.H., Choi H.S., Kim S.L., Lee D.S. Smit M.R., Ochomo E.O., Aljayyoussi G., Kwambai T.K., Abongo B.O., Chen T., Bousema T., Slater H.C., Waterhouse D., Bayoh N.M., Gimnig J.E., Samuels A.M., Desai M.R., Phillips-Howard P.A., Kariuki S.K., Wang D., Ward S.A., Ter Kuile F.O. Kumar R., Gururaj A.E., Barnes C.J. Hepatocellular carcinoma is the fourth leading cause of cancer death worldwide. There are still some problems that need to be studied and resolved before IVM is used in the clinic. Therefore, we believe that the anticancer effect of IVM is not limited to cytotoxicity, but also involves the regulation of the tumor microenvironment. Zhang P., Zhang Y., Liu K., Liu B., Xu W., Gao J., Ding L., Tao L. Ivermectin induces cell cycle arrest and apoptosis of HeLa cells via mitochondrial pathway. 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]. In addition, characteristic pyroptosis phenomena such as cell swelling and rupturing were observed. (2) IVM regulates the tumor microenvironment, inhibits the activity of tumor stem cells and reduces tumor angiogenesis and tumor metastasis. Background Discovery and development of novel drugs that are capable of overcoming drug resistance in tumor cells are urgently needed clinically. Several studies showed that the ivermectin has antitumor effects on a variety of cancer cells. Leukemia is a type of malignant clonal disease caused by abnormal hematopoietic stem cells [52]. Following the study, the FDA released a letter out of concern warning consumers not to self-medicate with ivermectin products intended for animals. Animal studies with rats given 3 times the maximum recommended human dose of 200 mcg/kg did not show any . JAMA Internal Medicine February 18, 2022. It is highly effective against many microorganisms including some viruses. Received 2020 Jun 5; Revised 2020 Sep 11; Accepted 2020 Sep 11. A study actually a review of trials done with ivermectin on COVID-19 patients claims large reductions in COVID-19 deaths are "possible using ivermectin.". However, whether ivermectin affects CRC is still unclear. Ivermectin (Systemic - Last updated on December 12, 2022 All rights owned and reserved by Memorial Sloan Kettering Cancer Center. Zheng Z., Li G. Mechanisms and Therapeutic Regulation of Pyroptosis in Inflammatory Diseases and Cancer. The latest research shows that in normal circumstances autophagy will prevent the induction of apoptosis and apoptosis-related caspase enzyme activation will inhibit autophagy. This may be related to the regulation of multiple signaling pathways by ivermectin through PAK1 kinase. It can be triggered by two activation pathways: the endogenous endoplasmic reticulum stress/mitochondrial pathway and the exogenous death receptor pathway [75,76]. B. MM, E.-S. AA Therapeutic potential of myrrh and ivermectin against experimental Trichinella spiralis infection in mice. Targeted treatment of key mutated genes in cancer, such as EGFR in lung cancer and HER2 in breast cancer, can achieve powerful clinical effects [105,106]. 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.
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