Niclosamide As a Promising Therapeutic Player in Human Cancer and Other Diseases

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Dec 23

PMID 36555754

Authors

Zhan Wang

Junyi Ren

Jinxiu Du

Huan Wang

Jia Liu

Guiling Wang

Affiliations

Soon will be listed here.

Abstract

Niclosamide is an FDA-approved anthelmintic drug for the treatment of parasitic infections. However, over the past few years, increasing evidence has shown that niclosamide could treat diseases beyond parasitic diseases, which include metabolic diseases, immune system diseases, bacterial and viral infections, asthma, arterial constriction, myopia, and cancer. Therefore, we systematically reviewed the pharmacological activities and therapeutic prospects of niclosamide in human disease and cancer and summarized the related molecular mechanisms and signaling pathways, indicating that niclosamide is a promising therapeutic player in various human diseases, including cancer.

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References

Chowdhury M, Turner N, Bentley N, Das A, Wu L, Richani D . Niclosamide reduces glucagon sensitivity via hepatic PKA inhibition in obese mice: Implications for glucose metabolism improvements in type 2 diabetes. Sci Rep. 2017; 7:40159. PMC: 5214666. DOI: 10.1038/srep40159. View

Choi H, Kim T, Lee S, Kim J, Ju Noh Y, Kim G . Bioanalysis of niclosamide in plasma using liquid chromatography-tandem mass and application to pharmacokinetics in rats and dogs. J Chromatogr B Analyt Technol Biomed Life Sci. 2021; 1179:122862. PMC: 8286234. DOI: 10.1016/j.jchromb.2021.122862. View

Yi Y, Woo Y, Hwang K, Kim H, Lee S . Niclosamide and Pyrvinium Are Both Potential Therapeutics for Osteosarcoma, Inhibiting Wnt-Axin2-Snail Cascade. Cancers (Basel). 2021; 13(18). PMC: 8464802. DOI: 10.3390/cancers13184630. View

De Francesco E, Ozsvari B, Sotgia F, Lisanti M . Dodecyl-TPP Targets Mitochondria and Potently Eradicates Cancer Stem Cells (CSCs): Synergy With FDA-Approved Drugs and Natural Compounds (Vitamin C and Berberine). Front Oncol. 2019; 9:615. PMC: 6692486. DOI: 10.3389/fonc.2019.00615. View

Jiao Y, Chen C, Hu X, Feng X, Shi Z, Cao J . Niclosamide and its derivative DK-520 inhibit RANKL-induced osteoclastogenesis. FEBS Open Bio. 2020; 10(8):1685-1697. PMC: 7396435. DOI: 10.1002/2211-5463.12921. View

Tao H, Zhang Y, Zeng X, Shulman G, Jin S . Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nat Med. 2014; 20(11):1263-9. PMC: 4299950. DOI: 10.1038/nm.3699. View

Taciak B, Pruszynska I, Kiraga L, Bialasek M, Krol M . Wnt signaling pathway in development and cancer. J Physiol Pharmacol. 2018; 69(2). DOI: 10.26402/jpp.2018.2.07. View

Xu J, Shi P, Li H, Zhou J . Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential. ACS Infect Dis. 2020; 6(5):909-915. PMC: 7098069. DOI: 10.1021/acsinfecdis.0c00052. View

Alasadi A, Chen M, Swapna G, Tao H, Guo J, Collantes J . Effect of mitochondrial uncouplers niclosamide ethanolamine (NEN) and oxyclozanide on hepatic metastasis of colon cancer. Cell Death Dis. 2018; 9(2):215. PMC: 5833462. DOI: 10.1038/s41419-017-0092-6. View

10.

Li Z, Xu J, Lang Y, Fan X, Kuo L, DBrant L . JMX0207, a Niclosamide Derivative with Improved Pharmacokinetics, Suppresses Zika Virus Infection Both and . ACS Infect Dis. 2020; 6(10):2616-2628. PMC: 7559020. DOI: 10.1021/acsinfecdis.0c00217. View

11.

Zhao D, Hu C, Fu Q, Lv H . Combined chemotherapy for triple negative breast cancer treatment by paclitaxel and niclosamide nanocrystals loaded thermosensitive hydrogel. Eur J Pharm Sci. 2021; 167:105992. DOI: 10.1016/j.ejps.2021.105992. View

12.

Abbott M, Ustoyev Y . Cancer and the Immune System: The History and Background of Immunotherapy. Semin Oncol Nurs. 2019; 35(5):150923. DOI: 10.1016/j.soncn.2019.08.002. View

13.

Rajamuthiah R, Fuchs B, Conery A, Kim W, Jayamani E, Kwon B . Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus. PLoS One. 2015; 10(4):e0124595. PMC: 4405337. DOI: 10.1371/journal.pone.0124595. View

14.

Cairns D, Boorgu D, Levin M, Kaplan D . Niclosamide rescues microcephaly in a humanized model of Zika infection using human induced neural stem cells. Biol Open. 2018; 7(1). PMC: 5829514. DOI: 10.1242/bio.031807. View

15.

Li J, Li H, Zhan D, Xiang M, Yang J, Zuo Y . Niclosamide sensitizes nasopharyngeal carcinoma to radiation by downregulating Ku70/80 expression. J Cancer. 2018; 9(4):736-744. PMC: 5858495. DOI: 10.7150/jca.20963. View

16.

Han P, Yuan C, Wang Y, Wang M, Weng W, Zhan H . Niclosamide ethanolamine protects kidney in adriamycin nephropathy by regulating mitochondrial redox balance. Am J Transl Res. 2019; 11(2):855-864. PMC: 6413276. View

17.

Giri A, Adhikari N, Khan K . Comparative genotoxicity of six salicylic acid derivatives in bone marrow cells of mice. Mutat Res. 1996; 370(1):1-9. DOI: 10.1016/s0165-1218(96)90121-4. View

18.

Xu J, Berastegui-Cabrera J, Chen H, Pachon J, Zhou J, Sanchez-Cespedes J . Structure-Activity Relationship Studies on Diversified Salicylamide Derivatives as Potent Inhibitors of Human Adenovirus Infection. J Med Chem. 2020; 63(6):3142-3160. DOI: 10.1021/acs.jmedchem.9b01950. View

19.

Hatamipour M, Jaafari M, A Momtazi-Borojeni A, Ramezani M, Sahebkar A . Nanoliposomal Encapsulation Enhances Anti-Tumor Activity of Niclosamide against Melanoma. Anticancer Agents Med Chem. 2019; 19(13):1618-1626. DOI: 10.2174/1871520619666190705120011. View

20.

Han P, Shao M, Guo L, Wang W, Song G, Yu X . Niclosamide ethanolamine improves diabetes and diabetic kidney disease in mice. Am J Transl Res. 2018; 10(4):1071-1084. PMC: 5934567. View