1. Ivermectin, a potential anticancer drug derived from an antiparasitic drug
- Author
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Fuying Cheng, Wei Zhang, Jiangyan Li, Qiang Fang, Yi Wang, Xiaodong Hu, Chenying Yu, Mingyang Tang, and Xin Yao
- Subjects
0301 basic medicine ,PRR, pattern recognition receptor ,SID, SIN3-interaction domain ,animal diseases ,ASC, Apoptosis-associated speck-like protein containing a CARD ,Review ,Pharmacology ,DAMP, Damage-associated molecular pattern ,0302 clinical medicine ,Ivermectin ,Neoplasms ,HBV, Hepatitis B virus ,HMGB1, High mobility group box-1 protein ,P-gp, P-glycoprotein ,Scabies ,PAK1, P-21-activated kinases 1 ,Molecular Targeted Therapy ,PAMP, Pathogen-associated molecular pattern ,media_common ,NAC, N-acetyl-L-cysteine ,GABA, Gamma-aminobutyric acid ,avermectin(PubChem CID：6434889) ,EBV, Epstein-Barr virus ,Antiparasitic Agents ,Cell Death ,moxidectin(PubChem CID：9832912) ,GSDMD, Gasdermin D ,LD50, median lethal dose ,Anticancer drug ,humanities ,Drug repositioning ,MDR, Multidrug resistance ,030220 oncology & carcinogenesis ,HER2, Human epidermal growth factor receptor 2 ,ivermectin(PubChem CID：6321424) ,EMT, Epithelial mesenchymal-transition ,selamectin(PubChem CID：9578507) ,Signal Transduction ,medicine.drug ,Drug ,Antiparasitic ,medicine.drug_class ,media_common.quotation_subject ,Antineoplastic Agents ,Elephantiasis ,drug repositioning ,HCV, Hepatitis C virus ,HSP27, Heat shock protein 27 ,ivermectin ,03 medical and health sciences ,IVM, Ivermectin ,YAP1, Yes-associated protein 1 ,parasitic diseases ,medicine ,EGFR, Epidermal growth factor receptor ,Animals ,Humans ,cancer ,ALCAR, acetyl-L-carnitine ,CSCs, Cancer stem cells ,doramectin(PubChem CID：9832750) ,LDH, Lactate dehydrogenase ,Blindness ,business.industry ,PARP, poly (ADP- ribose) polymerase ,TNBC, Triple-negative breast cancer ,medicine.disease ,OCT-4, Octamer-binding protein 4 ,STAT3, Signal transducer and activator of transcription 3 ,030104 developmental biology ,siRNA, small interfering RNA ,SOX-2, SRY-box 2 ,business ,ROS, Reactive oxygen species - Abstract
Graphical abstract Ivermectin has powerful antitumor effects, including the inhibition of proliferation, metastasis, and angiogenic activity, in a variety of cancer cells. This may be related to the regulation of multiple signaling pathways by ivermectin through PAK1 kinase. On the other hand, ivermectin promotes programmed cancer cell death, including apoptosis, autophagy and pyroptosis. Ivermectin induces apoptosis and autophagy is mutually regulated. 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., Highlights • Ivermectin effectively suppresses the proliferation and metastasis of cancer cells and promotes cancer cell death at doses that are nontoxic to normal cells. • Ivermectin shows excellent efficacy against conventional chemotherapy drug-resistant cancer cells and reverses multidrug resistance. • Ivermectin combined with other chemotherapy drugs or targeted drugs has powerful effects on cancer. • The structure of crosstalk centered on PAK1 kinase reveals the mechanism by which ivermectin regulates multiple signaling pathways. • Ivermectin has been used to treat parasitic diseases in humans for many years and can quickly enter clinical trials for the treatment of tumors., 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. Satoshi ōmura 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. Recently, ivermectin has been reported to inhibit the proliferation of several tumor cells by regulating multiple signaling pathways. This suggests that ivermectin may be an anticancer drug with great potential. Here, we reviewed the related mechanisms by which ivermectin inhibited the development of different cancers and promoted programmed cell death and discussed the prospects for the clinical application of ivermectin as an anticancer drug for neoplasm therapy.
- Published
- 2020