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Efficacy of auranofin as an inhibitor of desmoid progression
Kan Ito1, Yoshihiro Nishida2,3, Shunsuke Hamada4
1Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
Abstract:
Anticancer drugs and molecular targeted therapies are used for refractory desmoid-type fibromatosis (DF), but occasionally cause severe side effects. The purpose of this study was to identify an effective drug with fewer side effects against DF by drug repositioning, and evaluate its efficacy. FDA-approved drugs that inhibit the proliferation of DF cells harboring S45F mutations of CTNNB1 were screened. An identified drug was subjected to the investigation of apoptotic effects on DF cells with analysis of Caspase 3/7 activity. Expression of β-catenin was evaluated with western blot analysis, and immunofluorescence staining. Effects of the identified drug on in vivo DF were analyzed using Apc1638N mice. Auranofin was identified as a drug that effectively inhibits the proliferation of DF cells. Auranofin did not affect Caspase 3/7 activity compared to control. The expression level of β-catenin protein was not changed regardless of auranofin concentration. Auranofin effectively inhibited the development of tumorous tissues by both oral and intraperitoneal administration, particularly in male mice. Auranofin, an anti-rheumatic drug, was identified to have repositioning effects on DF. Since auranofin has been used for many years as an FDA-approved drug, it could be a promising drug with fewer side effects for DF.
Insights
Auranofin, an anti-rheumatic drug, shows promise for treating desmoid-type fibromatosis (DF). This repositioned drug effectively inhibits DF cell proliferation and tumor development with potentially fewer side effects than current therapies.
Area of Science:
- Oncology
- Pharmacology
- Drug Repurposing
Background:
- Refractory desmoid-type fibromatosis (DF) often requires treatment with anticancer drugs or molecular targeted therapies.
- These current treatments can lead to severe side effects, necessitating the search for safer alternatives.
Purpose of the Study:
- To identify an effective drug with a favorable side effect profile for desmoid-type fibromatosis (DF) through drug repositioning.
- To evaluate the efficacy of a repositioned drug in preclinical models of DF.
Main Methods:
- Screened FDA-approved drugs for their ability to inhibit proliferation of DF cells with CTNNB1 S45F mutations.
- Investigated the drug's apoptotic effects on DF cells and its impact on β-catenin expression.
- Assessed the drug's efficacy in inhibiting DF development in vivo using Apc1638N mice.
Main Results:
- Auranofin was identified as a drug that effectively inhibits DF cell proliferation.
- Auranofin did not significantly alter Caspase 3/7 activity or β-catenin protein levels.
- Auranofin administration inhibited tumorous tissue development in vivo, particularly in male mice.
Conclusions:
- Auranofin, an anti-rheumatic drug, demonstrates significant repositioning potential for treating desmoid-type fibromatosis (DF).
- As an existing FDA-approved medication, auranofin represents a promising therapeutic candidate with a potentially improved safety profile for DF management.
