Flubendazole and mebendazole impair migration and epithelial to mesenchymal transition in oral cell lines
Abstract
Benzimidazole anthelmintics flubendazole and mebendazole are microtubule-targeting drugs that showed considerable anti-cancer activity in different preclinical models. In this study, the effects of flubendazole and mebendazole on proliferation, migration and cadherin switching were studied in a panel of oral cell lines in vitro. Both compounds reduced the viability of the PE/CA-PJ15 and H376 oral squamous carcinoma cells and of the premalignant oral keratinocytes DOK with the IC 50 values in the range of 0.19-0.26 μM. Normal oral keratinocytes and normal gingival fibroblasts were less sensitive to the treatment. Flubendazole and mebendazole also reduced the migration of the PE/CA-PJ15 cell in concentrations that had no anti-migratory effects on the normal gingival fibroblasts. Levels of the focal adhesion kinase FAK, Rho-A and Rac1 GTPases and the Rho guanine nucleotide exchange factor GEF-H1 were decreased in both PE/CA-PJ15 cells and gingival fibroblasts following treatment. Both drugs also interfered with cadherin switching in the model of TGF-β-induced epithelial to mesenchymal transition (EMT) in the DOK cell line. Levels of N-cadherin were reduced in the TGF-β induced cells co-treated with flubendazol and mebendazole in very low concentration (50 nM). These results suggest direct effects of both benzimidazoles on selected processes of EMT in oral cell lines such as cadherin switching as well as cellular migration.
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In the TGF-β-induced dysplastic oral keratinocyte cell line, mebendazole disrupts cadherin equilibrium.
“in the TGF-β-induced dysplastic oral keratinocyte (DOK) cell line, which models EMT, MBZ was shown to disrupt the cadherin equilibrium”
From Drug repurposing for cancer therapy (2024) · cites this paper as [163]
In oral squamous cell carcinoma, mebendazole downregulates specific proteins and enzymes including FAK, Rho-A, and Rac1 GTPase.
“In oral squamous cell carcinoma, MBZ was found to downregulate specific proteins and enzymes, including FAK, Rho-A, and Rac1 GTPase.”
From Drug repurposing for cancer therapy (2024) · cites this paper as [163]
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References 50 · Cited by 30
- Authors
- Kralova, V., Hanušová, V., Caltová, K., Špaček, P., Hochmalová, M., Skálová, L., & Rudolf, E.
- Affiliations
- Charles University (CZ)
- Venue
- Chemico-Biological Interactions
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 293
- Pages
- 124-132
- ISSN
- 0009-2797 (ISSN-L)
- OpenAlex
- W2886635219
- Cited by
- 30
- References
- 50
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 2
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chemico-Biological Interactions (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Charles University (PROGRESS Q40/01)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- flubendazole, mebendazole, benzimidazole anthelmintics, oral squamous cell carcinoma, epithelial-mesenchymal transition, cell migration, cadherin switching, N-cadherin, TGF-beta, focal adhesion kinase, RhoA, Rac1, GEF-H1, microtubule inhibitors, oral keratinocytes, anticancer activity
- MeSH terms
- Carcinoma, Squamous Cell, Cell Line, Cell Movement, Humans, Mebendazole, Mouth Neoplasms, Cadherins, Transforming Growth Factor beta, rhoA GTP-Binding Protein, cdc42 GTP-Binding Protein, Cell Proliferation, Focal Adhesion Kinase 1, Epithelial-Mesenchymal Transition
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