A pharmacology-based comparison of the activity of albendazole and flubendazole against Echinococcus granulosus metacestode in sheep

Ceballos, Laura; Virkel, G.; Elissondo, Marı́a Celina; Cantón, Candela; Canevari, Jose Tobias; Murno, Graciela; Denegri, Guillermo M.; Lanusse, Carlos; Álvarez, Luis Ignacio Ortega

doi:10.1016/j.actatropica.2013.05.004

Cited by 23 publications

(11 citation statements)

References 47 publications

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“…Flubendazole has been extensively studied for antihelmintic use in animal and humans with favorable toxicology profiles [22, 25, 46]. Consistently, our data displayed that flubendazole treatment (25 mg/kg, daily) did not alter gaining weight of nude mice during the experiment compared with the control group (Fig.…”

Section: Discussionsupporting

confidence: 87%

“…However, poor absorption is still a challenge for clinical application of flubendazole [29]. Flubendazole produces low plasma concentrations in hosts due to its high lipophilicity [22, 24]. Recent studies report that solid dispersion technique and emulsion cross-linking volatile technique are utilized to enhance the bioavalibility of albendazole that has the similar absorption properties and structure with flubendazole [47-49].…”

Section: Discussionmentioning

confidence: 99%

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Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells

et al. 2015

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Cancer stem-like cell (CS-like cell) is considered to be responsible for recurrence and drug resistance events in breast cancer, which makes it a potential target for novel cancer therapeutic strategy. The FDA approved flubendazole, has been widely used in the treatment of intestinal parasites. Here, we demonstrated a novel effect of flubendazole on breast CS-like cells. Flubendazole inhibited breast cancer cells proliferation in dose- and time-dependent manner and delayed tumor growth in xenograft models by intraperitoneal injection. Importantly, flubendazole reduced CD44high/CD24low subpopulation and suppressed the formation of mammosphere and the expression of self-renewal related genes including c-myc, oct4, sox2, nanog and cyclinD1. Moreover, we found that flubendazole induced cell differentiation and inhibited cell migration. Consistently, flubendazole reduced mesenchymal markers (β-catenin, N-cadherin and Vimentin) expression and induced epithelial and differentiation marker (Keratin 18) expression in breast cancer cells. Mechanism study revealed that flubendazole arrested cell cycle at G2/M phase and induced monopolar spindle formation through inhibiting tubulin polymerization. Furthermore, flubendazole enhanced cytotoxic activity of conventional therapeutic drugs fluorouracil and doxorubicin against breast cancer cells. In conclusion, our findings uncovered a remarkable effect of flubendazole on suppressing breast CS-like cells, indicating a novel utilization of flubendazole in breast cancer therapy.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells

et al. 2015

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“…These changes may explain the change in ratio of red to green fluorescence observed in this work. An increase in pharmacological action after combination of Met with ABZ, a traditional antiparasitic agents [ 24 ], indicates inhibition of aggregation in the cytoplasmic microtubule system of the parasites, which blocks the uptake of a variety of nutrients and glucose, after crossing the tegumental system and to achieve the tissue distribution.…”

Section: Discussionmentioning

confidence: 99%

Construction of In Vivo Fluorescent Imaging of <i>Echinococcus granulosus</i> in a Mouse Model

et al. 2016

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Human hydatid disease (cystic echinococcosis, CE) is a chronic parasitic infection caused by the larval stage of the cestode Echinococcus granulosus. As the disease mainly affects the liver, approximately 70% of all identified CE cases are detected in this organ. Optical molecular imaging (OMI), a noninvasive imaging technique, has never been used in vivo with the specific molecular markers of CE. Thus, we aimed to construct an in vivo fluorescent imaging mouse model of CE to locate and quantify the presence of the parasites within the liver noninvasively. Drug-treated protoscolices were monitored after marking by JC-1 dye in in vitro and in vivo studies. This work describes for the first time the successful construction of an in vivo model of E. granulosus in a small living experimental animal to achieve dynamic monitoring and observation of multiple time points of the infection course. Using this model, we quantified and analyzed labeled protoscolices based on the intensities of their red and green fluorescence. Interestingly, the ratio of red to green fluorescence intensity not only revealed the location of protoscolices but also determined the viability of the parasites in vivo and in vivo tests. The noninvasive imaging model proposed in this work will be further studied for long-term detection and observation and may potentially be widely utilized in susceptibility testing and therapeutic effect evaluation.

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“…Oral treatment with ABZ over 55 days was also effective against the larval stage of E . granulosus in naturally infected sheep [ 91 ]. In this study, the vitality and in vivo development to cysts in mice of protoscoleces obtained from hydatid cysts recovered from treated animals was greatly reduced compared to protoscoleces obtained from unmedicated animals.…”

Section: Introductionmentioning

confidence: 99%

Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets

et al. 2018

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Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways.

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A pharmacology-based comparison of the activity of albendazole and flubendazole against Echinococcus granulosus metacestode in sheep

Cited by 23 publications

References 47 publications

Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells

Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells

Construction of In Vivo Fluorescent Imaging of <i>Echinococcus granulosus</i> in a Mouse Model

Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets

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