• BMB Reports
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• v.44 no.8
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• pp.517-522
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• 2011

Mitochondrial dynamics not only involves mitochondrial morphology but also mitochondrial biogenesis, mitochondrial distribution, and cell death. To identify specific regulators to mitochondria dynamics, we screened a chemical library and identified niclosamide as a potent inducer of mitochondria fission. Niclosamide promoted mitochondrial fragmentation but this was blocked by down-regulation of Drp1. Niclosamide treatment resulted in the disruption of mitochondria membrane potential and reduction of ATP levels. Moreover, niclosamide led to apoptotic cell death by caspase-3 activation. Interestingly, niclosamide also increased autophagic activity. Inhibition of autophagy suppressed niclosamide-induced cell death. Therefore, our findings suggest that niclosamide induces mitochondria fragmentation and may contribute to apoptotic and autophagic cell death.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.306-313
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• 2023

Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β. Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.

• Biomolecules & Therapeutics
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• v.31 no.5
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• pp.515-525
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• 2023

The most common heart valve disorder is calcific aortic valve stenosis (CAVS), which is characterized by a narrowing of the aortic valve. Treatment with the drug molecule, in addition to surgical and transcatheter valve replacement, is the primary focus of researchers in this field. The purpose of this study is to determine whether niclosamide can reduce calcification in aortic valve interstitial cells (VICs). To induce calcification, cells were treated with a pro-calcifying medium (PCM). Different concentrations of niclosamide were added to the PCM-treated cells, and the level of calcification, mRNA, and protein expression of calcification markers was measured. Niclosamide inhibited aortic valve calcification as observed from reduced alizarin red s staining in niclosamide treated VICs and also decreased the mRNA and protein expressions of calcification-specific markers: runt-related transcription factor 2 and osteopontin. Niclosamide also reduced the formation of reactive oxygen species, NADPH oxidase activity and the expression of Nox2 and p22^phox. Furthermore, in calcified VICs, niclosamide inhibited the expression of β-catenin and phosphorylated glycogen synthase kinase (GSK-3β), as well as the phosphorylation of AKT and ERK. Taken together, our findings suggest that niclosamide may alleviate PCM-induced calcification, at least in part, by targeting oxidative stress mediated GSK-3β/β-catenin signaling pathway via inhibiting activation of AKT and ERK, and may be a potential treatment for CAVS.

• Biomedical Science Letters
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• v.29 no.4
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• pp.382-385
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• 2023

NK (Natural killer) cells are innate immune cells and play important roles as the first immune cells to act when cancer occurs. In many cancer patients, NK cells can be seen to be inactivated, suggesting that NK cells are important in cancer treatment. In order to overcome the disadvantages of NK cells in cancer treatment, it is critical to develop strategies that enhance the proliferation and cytolytic function of NK cells. We applied niclosamide to measure the degree of NK cell activation, and obtained unexpected results of increased NK cell numbers and anti-tumor activity. Although further investigation is required to uncover the detailed mechanisms, our results suggest that Niclosamide is a promising candidate to increase the efficacy of cancer immunotherapy using NK cells.

• Journal of Life Science
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• v.28 no.10
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• pp.1212-1219
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• 2018

The critical role of heat shock protein 90 (Hsp90) in tumorigenesis led to the development of several first- and second-generation Hsp90 inhibitors, which have demonstrated promising responses in cancers. In this study, we found second-generation Hsp90 inhibitor BIIB021-resistant multidrug-resistant (MDR) human cancer cells, although BIIB021 was shown to be active in first-generation Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-resistant MDR cells. MCF7-MDR and HeyA8- MDR cells were more resistant to BIIB021 than their parental counterparts, indicating that BIIB021 cannot be applicable to all cancer cells expressing MDR proteins. We revealed that dimethyl-celecoxib (DMC), one of the non-steroidal anti-inflammatory drugs (NSAIDs), potentiated cytotoxicity of BIIB021 against both BIIB021-resistant and BIIB021-sensitive MDR cells. The effectiveness of NSAIDs involving celecoxib and DMC in combination with BIIB021 led to the autophagic degradation/down-regulation of mutant p53 (mutp53) that overexpressed MDR cells and the suppression of Hsp70 induction. This resulted in sensitization of MDR cells to BIIB021. Moreover, autophagy induction by sulindac sulfide, another type of NSAID, and niclosamide, an FDA-approved anthelmintic drug, potentiated 17-AAG-mediated autophagic degradation/down-regulation of mutp53 and c-Myc, client proteins of Hsp90. Therefore, our results suggest that NSAIDs and niclosamide positively enhance the anticancer activity of Hsp90 inhibitors through an autophagic pathway. They may also be new candidates for sensitizing MDR cells to Hsp90 inhibitors.

• The Korean Journal of Malacology
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• v.14 no.2
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• pp.85-90
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• 1998

The effects of methanol extracts of plant molluscicide, Brassaia actinophylla (Araliaceae) had been assessed on development of eggs f snails, Biomphalaria glabrata and Indoplanorbis exustus at sublethal concentrations. Results revealed that the administration of 10mg/l of B. actionophylla caused some alterations in embryos of both species. Niclosamide (0.004 mg/l) also arrested the development of embryos in B. glabrata ans I. exustus. It can be concluded that B. actinophylla has a potential use as an avicidal agent in the control of the snail intermediate hosts of schistosomiasis.

• Korean Journal of Crystallography
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• v.4 no.1
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• pp.1-5
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• 1993

The crystal structure of N-(2'-chloro-4'-vitrophenyl)-5-chlorosalicylamide( Niclosamide ) monohydrate has been determined from 1976 sig- nificant independent reflections collected on an automated CAD4 diffractometer using graphitemonochromated Mo-Ka radiation. The crystal is monoclinic, space group P211c, with unit cell dimensions, a=11.331 (3), b=16.964(2), c=7.347(4)A , P =98.20(3)° and Z=4 at T=293k. The structure was solved by direct method using seminvariants of ggg Parity group and refined by the full-matrix least-square method, resulting model with reliability factor, R=0.046. The feature of the molecule show planar structure in parallel to the ab crystal plane.

• Parasites, Hosts and Diseases
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• v.51 no.5
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• pp.537-544
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• 2013

The present study was performed to observe histopathological changes in tissues of Bithynia siamensis goniomphalos (Gastropoda, Bithyniidae) incubated in crude extract solutions of camellia (Camellia oleifera) seed and mangosteen (Garcinia mangostana) pericarp, and furthermore to estimate the molluscicidal effects of 2 plant substances. Substantial numbers of bithyniid snails were incubated in various concentrations of 2 plant solution for 24 hr. As the positive control, snails incubated in various concentrations of niclosamide, a chemical molluscicide, were used. The histopathological findings were observed in sectioned snail specimens of each experimental and control groups. The results showed that both camellia and mangosteen extracts had molluscicidal effects at 24 hr with 50% lethal concentration ($LC_{50}$) at concentrations of 0.003 and 0.002 g/ml, respectively, while niclosamide had $LC_{50}$ at concentrations 0.599 ppm. B. siamensis goniomphalos snail tissues (foot, gill, and digestive system) showed disruption of columnar muscle fibers of the foot, reduction of the length and number of gill cilia, numerous mucous vacuoles, and irregularly shaped of epithelial cells. Irregular apical and calciferous cells, dilatation of the digestive gland tubule, and large hemolymphatic spaces, and irregular apical surfaces, detachment of cilia, and enlargement of lysosomal vacuoles of epidermis were also shown in all groups. By the present study, it is confirmed that 2 plants, camellia and mangosteen, are keeping some substance having molluscicidal effects, and histopathological findings obtained in this study will provide some clues in further studies on their action mechanisms to use them as natural molluscicides.

• Parasites, Hosts and Diseases
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• v.21 no.2
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• pp.150-156
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• 1983

Five cases of Diphyllobothrium latum infection were proved by collection of worms after treatment with bithionol, niclosamide or praziquantel, during 1975~1983. The patients were 4 males and one female aged 10~64 years residing in Seoul or Wando-gun, Chollanam-do, Korea. All of them remembered the history of eating several kinds of raw marine fish and 2 persons said they ate the raw mesh of perch, Lateolabrax japcnicus. Three amcnE them experienced abdominal pain, 2 natural discharge of a chain of segments, but none revealed any sign of anemia. The average egg size in stool varied $59~67{\times}41~48{\mu\textrm{m}}$ according to cases. The eggs were characterised by ovoid to elliptical shape, terminal operculum, and distinct abopercular protuberance. One naturally discharged segment (30cm) and 4 complete strobilae (320~680cm) with scolices obtained after treatments were examined. The morphological characters of proglottids such as rosette-form uterus with 3~6 loops, vaginal pore included in the cirrus sac, separated seminal vesicle from cirrus sac, etc. were all compatible with D. latum. These are the 7th~11th cases of D. latum infection proved by worms in Korea.

• Parasites, Hosts and Diseases
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• v.30 no.2
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• pp.147-150
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• 1992

The second case of human infection with Mesccestoides Zineatus in Korea was reported. The patient, a farm worker, complained of abdominal pain and massive discharge of sesame-like proglottids in his stool for several months. Worms, recovered by chemotherapy with niclosamide, consisted of 32 strobilae. This may be the heaviest worm burden in human infection ever reported. The infected man habitually ate the raw viscera of chickens.