Successful treatment of acute fascioliasis with bithionol

Bacq, Yannick; Besnier, Jean-Marc; Duong, T.H.; Pavie, G.; Metman, É.-H.; Choutet, P.

doi:10.1002/hep.1840140620

Cited by 42 publications

(19 citation statements)

References 17 publications

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“…In fact, these compounds may be of use for the veterinary treatment of Avian Polyomavirus, which can cause acute death in a wide range of psittacine birds (Katoh et al, 2010). Further, in geographical regions where fluke outbreaks in humans are more problematic, bithionol has been used to successfully clear infections in humans after oral administration (Bacq et al, 1991; Kim, 1970; Lee and Kim, 2006; Price et al, 1993; Seo et al, 1982). …”

Section: Discussionmentioning

confidence: 99%

A screen for modulators of large T antigen’s ATPase activity uncovers novel inhibitors of Simian Virus 40 and BK virus replication

et al. 2012

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New polyomaviruses are continually being identified, and it is likely that links between this virus family and disease will continue to emerge. Unfortunately, a specific treatment for polyomavirus-associated disease is lacking. Because polyomaviruses express large Tumor Antigen, TAg, we hypothesized that small molecule inhibitors of the essential ATPase activity of TAg would inhibit viral replication. Using a new screening platform, we identified inhibitors of TAg's ATPase activity. Lead compounds were moved into a secondary assay, and ultimately two FDA approved compounds, bithionol and hexachlorophene, were identified as the most potent TAg inhibitors known to date. Both compounds inhibited Simian Virus 40 replication as assessed by plaque assay and quantitative PCR. Moreover, these compounds inhibited BK virus, which causes BKV Associated Nephropathy. In neither case was host cell viability compromised at these concentrations. Our data indicate that directed screening for TAg inhibitors is a viable method to identify polyomavirus inhibitors, and that bithionol and hexachlorophene represent lead compounds that may be further modified and/or ultimately used to combat diseases associated with polyomavirus infection.

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Section: Discussionmentioning

confidence: 99%

A screen for modulators of large T antigen’s ATPase activity uncovers novel inhibitors of Simian Virus 40 and BK virus replication

et al. 2012

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“…These studies also point the way to in vivo studies, as one of the lead compounds (bithionol) has received Food and Drug Administration approval as a second-line orally administered medication for the treatment of helminthic infection that can be safely dosed in humans at 25 mg kg À1 body weight per day (46). Detailed toxicology and pharmacokinetics on the drug are available, and oral doses of 50 mg/kg in three divided alternate daily doses for 5 days maintain serum levels in the range of 140 to 550 Amol/L in rabbits, dogs, and humans, or several times greater than those required to observe a 50% inhibition of melanoma cell migration in our in vitro assays.…”

Section: Discussionmentioning

confidence: 99%

Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion

Saunders

Ouellette

Bandle

et al. 2008

Molecular Cancer Therapeutics

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Autotaxin (ATX) is a prometastatic enzyme initially isolated from the conditioned medium of human melanoma cells that stimulates a myriad of biological activities, including angiogenesis and the promotion of cell growth, survival, and differentiation through the production of lysophosphatidic acid (LPA). ATX increases the aggressiveness and invasiveness of transformed cells, and ATX levels directly correlate with tumor stage and grade in several human malignancies. To study the role of ATX in the pathogenesis of malignant melanoma, we developed antibodies and small-molecule inhibitors against recombinant human protein. Immunohistochemistry of paraffinembedded human tissue shows that ATX levels are markedly increased in human primary and metastatic melanoma relative to benign nevi. Chemical screens identified several small-molecule inhibitors with binding constants ranging from nanomolar to low micromolar. Cell migration and invasion assays with melanoma cell lines show that ATX markedly stimulates melanoma cell migration and invasion, an effect suppressed by ATX inhibitors. The migratory phenotype can be rescued by the addition of the enzymatic product of ATX, LPA, confirming that the observed inhibition is linked to suppression of LPA production by ATX. Chemical analogues of the inhibitors show structure-activity relationships important for ATX inhibition and indicate pathways for their optimization. These studies suggest that ATX is an approachable molecular target for the rational design of chemotherapeutic agents directed against malignant melanoma. [Mol Cancer Ther 2008;7(10):3352 -62]

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“…In the present study, we investigated the novel combination of cisplatin with Bithionol [2, 2′-Sulfanediylbis (4, 6-dichlorophenol)] (BT) as an alternate therapeutic strategy. BT is a Food and Drug Administration-approved antiparasitic agent that has been safely dosed in humans to be used orally as a second-line medication for the treatment of helminthic infections [25]. Previously, we showed that BT exerts cytotoxic effects on a panel of ovarian cancer cell lines regardless of their cisplatin sensitivities [26].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the cytotoxicity of the Bithionol - cisplatin combination in a panel of human ovarian cancer cell lines

et al. 2017

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BackgroundCombination drug therapy appears a promising approach to overcome drug resistance and reduce drug-related toxicities in ovarian cancer treatments. In this in vitro study, we evaluated the antitumor efficacy of cisplatin in combination with Bithionol (BT) against a panel of ovarian cancer cell lines with special focus on cisplatin-sensitive and cisplatin-resistant cell lines. The primary objectives of this study are to determine the nature of the interactions between BT and cisplatin and to understand the mechanism(s) of action of BT-cisplatin combination.MethodsThe cytotoxic effects of drugs either alone or in combination were evaluated using presto-blue assay. Cellular reactive oxygen species were measured by flow cytometry. Immunoblot analysis was carried out to investigate changes in levels of cleaved PARP, XIAP, bcl-2, bcl-xL, p21 and p27. Luminescent and colorimetric assays were used to test caspases 3/7 and ATX activity.ResultsThe efficacy of the BT-cisplatin combination depends upon the cell type and concentrations of cisplatin and BT. In cisplatin-sensitive cell lines, BT and cisplatin were mostly antagonistic except when used at low concentrations, where synergy was observed. In contrast, in cisplatin-resistant cells, BT-cisplatin combination treatment displayed synergistic effects at most of the drug ratios/concentrations. Our results further revealed that the synergistic interaction was linked to increased reactive oxygen species generation and apoptosis. Enhanced apoptosis was correlated with loss of pro-survival factors (XIAP, bcl-2, bcl-xL), expression of pro-apoptotic markers (caspases 3/7, PARP cleavage) and enhanced cell cycle regulators p21 and p27.ConclusionIn cisplatin-resistant cell lines, BT potentiated cisplatin-induced cytotoxicity at most drug ratios via enhanced ROS generation and modulation of key regulators of apoptosis. Low doses of BT and cisplatin enhanced efficiency of cisplatin treatment in all the ovarian cancer cell lines tested. Our results suggest that novel combinations such as BT and cisplatin might be an attractive therapeutic approach to enhance ovarian cancer chemosensitivity. Combining low doses of cisplatin with subtherapeutic doses of BT can ultimately lead to the development of an innovative combination therapy to reduce/prevent the side effects normally occurring when high doses of cisplatin are administered.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-3034-2) contains supplementary material, which is available to authorized users.

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Successful treatment of acute fascioliasis with bithionol

Cited by 42 publications

References 17 publications

A screen for modulators of large T antigen’s ATPase activity uncovers novel inhibitors of Simian Virus 40 and BK virus replication

A screen for modulators of large T antigen’s ATPase activity uncovers novel inhibitors of Simian Virus 40 and BK virus replication

Identification of small-molecule inhibitors of autotaxin that inhibit melanoma cell migration and invasion

Evaluation of the cytotoxicity of the Bithionol - cisplatin combination in a panel of human ovarian cancer cell lines

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