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

Wang, Zhan; Ren, Junyi; Du, Jinxiu; Wang, Huan; Liu, Jia; Wang, Guiling

doi:10.3390/ijms232416116

Cited by 25 publications

(12 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous studies have highlighted niclosamide's anticancer effects, attributing them to apoptosis, inhibition of migration, invasion, and proliferation [26]. Our results further emphasize niclosamide as a potent TKT inhibitor, significantly reducing TKT activity and, consequently, suppressing T-ALL cell proliferation and tumor growth.…”

Section: Discussionsupporting

confidence: 73%

Regulating TKT activity inhibits proliferation of human acute lymphoblastic leukemia cells

Huang

2024

Am J Cancer Res

View full text Add to dashboard Cite

Among pediatric blood cancers, acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy. Within ALL, T-cell acute lymphoblastic leukemia (T-ALL) accounts for 10 to 15% of all pediatric cases, and ~25% of adult cases. For T-ALL, its recurrence and relapse after treatment remain problematic. Therefore, it is necessary to develop new therapies for T-ALL. Recent studies suggested regulating energy metabolism is a novel approach to inhibit tumor growth, likely a promising treatment. Transketolase (TKT) is an important enzyme for modulating glucose metabolize in the pentose phosphate pathway (PPP). In this study, we treated T-ALL cells with different doses of niclosamide and primary T-ALL PBMCs were analyzed by RNA sequencing. T-ALL cells treated with niclosamide were analyzed with the Western blotting and TKT activity assay. Metabolism of T-ALL cells was evaluated by ATP assay and seahorse analyses. Lastly, we used a T-ALL xenograft murine model to determine effects of TKT knockdown on T-ALL tumor growth. Tumor samples were analyzed by H&E and IHC stainings. We found that niclosamide reduced T-ALL cell viability, and reduced expressions of TKT, Transketolase-Like Protein 1/2 (TKTL1/2) and transaldolase. In addition, niclosamide inhibited TKT enzyme activity, aerobic metabolism and glycolysis, finally leading to lower production of ATP. TKT knockdown inhibited tumor growth of xenograft T-ALL mice. Findings showed that niclosamide inhibits T-ALL cell growth by inhibiting TKT and energy metabolism.

show abstract

Section: Discussionsupporting

confidence: 73%

Regulating TKT activity inhibits proliferation of human acute lymphoblastic leukemia cells

Huang

2024

Am J Cancer Res

View full text Add to dashboard Cite

show abstract

“…The present data demonstrate inhibition of mucus production/secretion by niclosamide and benzbromarone in airways and gut, yet the described effects on intracellular Ca 2+ may prevent their use in asthma and CF, or other diseases such as COVID-19, polycystic kidney disease, or cancer 55 . It should be considered that niclosamide is on the WHO list of essential medicines and is very well tolerated when applied orally at the standard dose of 2 g/day, which leads to plasma concentrations used in the present study 30 .…”

Section: Discussionmentioning

confidence: 58%

Inhibition of mucus secretion by niclosamide and benzbromarone in airways and intestine

Ousingsawat,

Centeio,

Reyne

et al. 2024

Sci Rep

View full text Add to dashboard Cite

The Ca2+ activated Cl− channel TMEM16A (anoctamin 1; ANO1) is expressed in secretory epithelial cells of airways and intestine. Previous studies provided evidence for a role of ANO1 in mucus secretion. In the present study we investigated the effects of the two ANO1-inhibitors niclosamide (Niclo) and benzbromarone (Benz) in vitro and in vivo in mouse models for cystic fibrosis (CF) and asthma. In human CF airway epithelial cells (CFBE), Ca2+ increase and activation of ANO1 by adenosine triphosphate (ATP) or ionomycin was strongly inhibited by 200 nM Niclo and 1 µM Benz. In asthmatic mice airway mucus secretion was inhibited by intratracheal instillation of Niclo or Benz. In homozygous F508del-cftr mice, intestinal mucus secretion and infiltration by CD45-positive cells was inhibited by intraperitoneal injection of Niclo (13 mg/kg/day for 7 days). In homozygous F508del-cftr rats intestinal mucus secretion was inhibited by oral application of Benz (5 mg/kg/day for 60 days). Taken together, well tolerated therapeutic concentrations of niclosamide and benzbromarone corresponding to plasma levels of treated patients, inhibit ANO1 and intracellular Ca2+ signals and may therefore be useful in inhibiting mucus hypersecretion and mucus obstruction in airways and intestine of patients suffering from asthma and CF, respectively.

show abstract

“…For example, as shown in Fig. 1, Oxyclozanide, 16 Closantel 17 was discovered to be a powerful antistaphylococcal, [18][19][20][21] Rafoxanide 22 was successful for the treatment of F. hepatica infection in cattle and sheep, and Niclosamide, was approved by FDA as an antihelmintic drug, 23,24 highly potent for treatment of COVID-19 and SARS-CoV-2 (ref. [25][26][27][28] and has high anti-cancer activity.…”

Section: Introductionmentioning

confidence: 99%

Microwave-assisted chemoselective synthesis and photophysical properties of 2-arylazo-biphenyl-4-carboxamides from hydrazonals

Alazemi,

Dawood,

Al-Matar

et al. 2023

RSC Adv.

View full text Add to dashboard Cite

show abstract

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

Cited by 25 publications

References 125 publications

Regulating TKT activity inhibits proliferation of human acute lymphoblastic leukemia cells

Regulating TKT activity inhibits proliferation of human acute lymphoblastic leukemia cells

Inhibition of mucus secretion by niclosamide and benzbromarone in airways and intestine

Microwave-assisted chemoselective synthesis and photophysical properties of 2-arylazo-biphenyl-4-carboxamides from hydrazonals

Contact Info

Product

Resources

About