Halofuginone: From veterinary use to human therapy

Pines, Mark; Vlodavsky, Israël; Nagler, Arnon

doi:10.1002/1098-2299(200007/08)50:3/4<371::aid-ddr19>3.0.co;2-r

Cited by 40 publications

(10 citation statements)

References 49 publications

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“…One antifibrotic agent is halofuginone, a small alkaloid molecule isolated from the plant Dichora febrifuga , that has been used as a coccidiostat in chickens since the 1960s (14). Coccidiostats are commonly added to the feed or water of poultry to prevent infection of the gastrointestinal tract by coccidium protozoa.…”

Section: Introductionmentioning

confidence: 99%

The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells

Grudzień

Low

Manning

et al. 2010

Fertility and Sterility

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Objective-To investigate the effects of the antifibrotic drug halofuginone on extracellular matrix production, cell proliferation and apoptosis of cultured myometrial and leiomyoma smooth muscle cells. Design-Comparative and controlled experimental research study. Setting-University research laboratory.Patients-Leiomyoma and myometrial tissues were obtained from 8 different patients at the time of elective hysterectomy.Main Outcome Measures-The effects of halofuginone on cell proliferation were assessed by tritiated thymidine uptake assays and cell count assays. Effects on TGFβ1, collagen type I, and collagen type III mRNA levels were assessed by quantitative real-time PCR. Effects on apoptosis were assayed using a chemiluminescent assay to measure changes in caspase 3 and 7.Results-Halofuginone inhibited cell proliferation of both leiomyoma and autologous myometrial cells in a dose-dependent manner by inhibiting DNA synthesis within 24 hrs and later inducing apoptosis (as measured by increased caspase 3/7) by 48-72 hrs. Halofuginone also significantly reduced collagen type I (α1) and collagen type III (α1) mRNA levels, as well as the profibrotic factor TGFβ1 mRNA levels in both cell types.Conclusions-These results provide evidence to support the use of the antifibrotic drug halofuginone as a novel drug treatment for uterine leiomyomas. Please address all correspondence to: Romana A. Nowak, 1207 W. Gregory Drive, Urbana, IL 61801, Tel: 217-244-3902, Fax: 217-333-8286, ranowak@uiuc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access INTRODUCTIONUterine leiomyomas are benign tumors originating from a single neoplastic uterine smooth muscle cell (SMC) and are characterized by an excess of extracellular matrix (ECM) production and increased cell proliferation. Although benign, these tumors present a significant health problem to women of reproductive age. Leiomyomas have a reported symptomatic prevalence of up to 25%, but the overall incidence of these tumors in premenopausal women has been reported to be as high as 77% (1-3). Nearly $1.5 billion healthcare dollars are spent yearly towards treatment of these benign tumors that cause abnormal uterine bleeding, severe abdominal pain and pressure, and infertility (4). Available treatments for leiomyomas are limited. Hysterectomy is considered the standard surgical treatment, but less-invasive treatments such as vaginal hysterectomy, laparoscopic excision, uterine artery embolization, and thermoblative therapy have become more common. Unfortunately, these are often followed by a high rate of recurrenc...

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Section: Introductionmentioning

confidence: 99%

The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells

Grudzień

Low

Manning

et al. 2010

Fertility and Sterility

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“…Halofuginone, an inhibitor of collagen type I synthesis [23,24], has been found to inhibit the gene expression of collagen type a1(I) but not of type II [25] or type III [26]. In culture, halofuginone attenuated collagen a1(I) gene expression by murine, avian and human skin fibroblasts derived from scleroderma and chronic graft-versus-host disease (cGvHD) patients [27].…”

Section: Introductionmentioning

confidence: 99%

Halofuginone, an inhibitor of collagen synthesis by rat stellate cells, stimulates insulin-like growth factor binding protein-1 synthesis by hepatocytes

Gnainsky

Spira

Paizi

et al. 2004

Journal of Hepatology

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“…Halofuginone hydrobromide is a synthesized analog of febrifugine, which is extracted from the leaf and root of traditional Chinese herbal Dichroa febrifuga Lour. Since ancient times the herb D. febrifuga L. has been used in traditional Chinese medicine as an anti malarial treatment (Pines et al 2000). The extracts from roots and leaves of D. febrifuga L. including febrifugine, have been also used to protect chickens from infection with Plasmodium gallinaceum and malaria (Jang et al 1948).…”

Section: Introductionmentioning

confidence: 99%

“…Tang and Eisenbrand (1992) demonstrated that febrifugine had a higher anti-malarial activity than quinine against Plasmodium lophurae, P. gallinaceum and Plasmodium cynomolgi. Halofuginone is also used in human therapies for systemic sclerosis of the skin and internal organs where it inhibits collagen α1 (Ι) gene expression and collagen synthesis (Dorne et al 2011;Granot et al 1991;Pines et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Anticoccidial effect of halofuginone hydrobromide against Eimeria tenella with associated histology

et al. 2012

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Halofuginone (stenorol) has been used as an effective anticoccidial reagent for decades but very little is known about its mode of action. In this study, chickens were inoculated with Eimeria tenella oocysts on 14-day-old and medicated with halofuginone at days 0, 1, 2, 3, 4, 5 and 6 post inoculations (groups 0, 1, 2, 3, 4, 5 and 6, respectively). Chickens in group 7 were taken as challenge-unmedicated control and in group 8 unchallenged-unmedicated control. The survival rate, body weight gains (BWG), oocysts production, cecal scores, bloody diarrhea and histological examinations were analyzed to evaluate the anticoccidial efficacy of halofuginone and to initially elucidate its mechanisms. Results showed that halofuginone which acted as a coccidiostatic can significantly enhance the BWG, and decrease both the oocyst shedding and cecal destruction caused by E. tenella infection. The histological slide examination noted that halofuginone was effective when provided 0-2 days post inoculation but only partially effective when applied 3-7 days post infection. The second-generation schizonts treated with halofuginone appeared vacuolated and degenerated. It is concluded that halofuginone can inhibit the parasite's invasion of host cecal hypothetical cell at the early stages of life cycle and later disturb the parasite's development by vacuolation of the schizonts. The resulting abnormal schizonts could not divide into schizoites and were eventually eliminated by the host's immune response.

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Halofuginone: From veterinary use to human therapy

Cited by 40 publications

References 49 publications

The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells

The antifibrotic drug halofuginone inhibits proliferation and collagen production by human leiomyoma and myometrial smooth muscle cells

Halofuginone, an inhibitor of collagen synthesis by rat stellate cells, stimulates insulin-like growth factor binding protein-1 synthesis by hepatocytes

Anticoccidial effect of halofuginone hydrobromide against Eimeria tenella with associated histology

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