Catalysis of NADH→NADP+ transhydrogenation by adult Hymenolepis diminuta mitochondria

Park, J. P.; Fioravanti, Carmen F.

doi:10.1007/s00436-005-0020-z

Cited by 14 publications

(17 citation statements)

References 35 publications

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“…Although niclosamide was proposed to kill parasitic helminths by uncoupling oxidative phosphorylation and disrupting NADH→NADP + transhydrogenation (28,29), we discovered that niclosamide causes a striking increase in ROS in human cancer cells, which at least partially contributes to the onset of apoptosis. We also showed that ROS elevation and NF-κB inactivation may be independent biological activities of niclosamide.…”

Section: Discussionmentioning

confidence: 90%

“…Niclosamide was reported to inhibit the NADH→NADP + transhydrogenation on Hymenolepis diminuta submitochondrial particle assay (28,29). We therefore assessed whether niclosamide induced intracellular ROS generation.…”

Section: Resultsmentioning

confidence: 98%

“…The mechanisms of its action remained elusive, although it seems to inhibit mitochondrial oxidative phosphorylation of these worms (28,29). Niclosamide has low toxicity in mammals (oral LD 50 in rats, >5,000 mg/kg; ref.…”

Section: Discussionmentioning

confidence: 99%

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Antineoplastic Mechanisms of Niclosamide in Acute Myelogenous Leukemia Stem Cells: Inactivation of the NF-κB Pathway and Generation of Reactive Oxygen Species

Jin

Lu²,

Ding³

et al. 2010

Cancer Research

300

305

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NF-κB may be a potential therapeutic target for acute myelogenous leukemia (AML) because NF-κB activation is found in primitive human AML blast cells. In this report, we initially discovered that the potent antineoplastic effect of niclosamide, a Food and Drug Administration-approved antihelminthic agent, was through inhibition of the NF-κB pathway in AML cells. Niclosamide inhibited the transcription and DNA binding of NF-κB. It blocked tumor necrosis factor-induced IκBα phosphorylation, translocation of p65, and expression of NF-κB-regulated genes. Niclosamide inhibited the steps TAK1→IκB kinase (IKK) and IKK→IκBα. Niclosamide also increased the levels of reactive oxygen species (ROS) in AML cells. Quenching ROS by the glutathione precursor N-acetylcysteine attenuated niclosamide-induced apoptosis. Our results together suggest that niclosamide inhibited the NF-κB pathway and increased ROS levels to induce apoptosis in AML cells. On translational study of the efficacy of niclosamide against AML, niclosamide killed progenitor/stem cells from AML patients but spared those from normal bone marrow. Niclosamide was synergistic with the frontline chemotherapeutic agents cytarabine, etoposide, and daunorubicin. It potently inhibited the growth of AML cells in vitro and in nude mice. Our results support further investigation of niclosamide in clinical trials of AML patients. Cancer Res; 70(6); 2516-27. ©2010 AACR.

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Section: Discussionmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 98%

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Antineoplastic Mechanisms of Niclosamide in Acute Myelogenous Leukemia Stem Cells: Inactivation of the NF-κB Pathway and Generation of Reactive Oxygen Species

Jin

Lu²,

Ding³

et al. 2010

Cancer Research

300

305

View full text Add to dashboard Cite

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“…Niclosamide functions to inhibit NADH→NADP+ transhydrogenation driven by electron transport-dependent NADH oxidation and increases ROS level (18). Excessive ROS disrupts the mitochondrial permeability transition that is an important step for the induction of mitochondria-mediated cell death.…”

Section: Niclosamide Induces Mitochondrial Dysfunctions In Hela Cellsmentioning

confidence: 99%

Niclosamide induces mitochondria fragmentation and promotes both apoptotic and autophagic cell death

Park

Shin²,

Kang³

et al. 2011

BMB Reports

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“…В России известен под названием фенасал [1]. Показано, что никлозамид является разобщителем дыхания и окислительного фосфорилирования в митохондриях ленточных гельминтов [2], улиток [3] и опухолевых клеток [4].…”

Section: никлозамидunclassified

Molecular mechanisms of niclosamide antitumor activity

et al. 2015

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In this review the recent data regarding the antitumor activity of niclosamide and the molecular mechanisms of its antitumor activity are presented. Niclosamide has been used in the clinic for the treatment of intestinal parasite infections. In recent years in several screening investigations of various drugs and chemical compounds niclosamide was identified as a potential anticancer agent. Niclosamide not only inhibits the Wnt/b-catenin, mTORC1, STAT3, NF-kB and Notch signaling pathways, but also targets mitochondria in cancer cells to induce growth inhibition and apoptosis. A number of studies have established the anticancer activity of niclosamide in both in vitro and in vivo in xenotransplantation models using human tumors and immunodeficient mice. It is important that niclosamide is active not only against tumor cells but also cancer stem cells. Normal cells are resistant to niclosamide. The accumulated experimental data suggest niclosamide is a promising drug for the treatment of various types of cancer.

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Catalysis of NADH→NADP+ transhydrogenation by adult Hymenolepis diminuta mitochondria

Cited by 14 publications

References 35 publications

Antineoplastic Mechanisms of Niclosamide in Acute Myelogenous Leukemia Stem Cells: Inactivation of the NF-κB Pathway and Generation of Reactive Oxygen Species

Antineoplastic Mechanisms of Niclosamide in Acute Myelogenous Leukemia Stem Cells: Inactivation of the NF-κB Pathway and Generation of Reactive Oxygen Species

Niclosamide induces mitochondria fragmentation and promotes both apoptotic and autophagic cell death

Molecular mechanisms of niclosamide antitumor activity

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