Mebendazole Impedes the Proliferation and Migration of Pancreatic Cancer Cells through SK1 Inhibition Dependent Pathway
Open accessAbstract
Pancreatic ductal adenocarcinoma (PDAC) has one of the highest mortality rates and requires the development of highly efficacious medications that can improve the efficiency of existing treatment methods. In particular, in PDAC, resistance to conventional chemotherapy reduces the effectiveness of anticancer drugs, decreasing the therapeutic efficiency. Sphingosine 1-phosphate (S1P), produced by sphingosine kinase (SK), plays a vital role in cancer growth, metastasis, chemotherapy, and drug resistance. Focusing on the structural characteristics of mebendazole (MBZ), we studied whether MBZ would affect metastasis, invasion, and drug resistance in cancer by lowering S1P production through inhibition of SK activity. MBZ selectively inhibited SK1 more than SK2 and regulated the levels of sphingolipids. MBZ inhibited the proliferation and migration of cancer cells in other PDAC cell lines. To determine whether the effect of MBZ on cancer cell growth and migration is S1P-mediated, S1P was treated, and the growth and migration of cancer cells were observed. It was found that MBZ inhibited S1P-induced cancer cell growth, and MBZ showed a growth inhibitory effect by regulating the JAK2/STAT3/Bcl-2 pathway. The phosphorylation of focal adhesion kinase (FAK), a transcription factor that regulates migration, was inhibited by MBZ, so it was found that the effect of MBZ regulates the migration of cancer cells through the S1P/FAK/vimentin pathway. In conclusion, our study suggests that the anthelmintic MBZ can be used as a potential therapeutic agent for treating PDAC and for structural synthesis studies of its analogs.
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Mebendazole might modulate cancer cell migration through the S1P/FAK/vimentin pathway.
“other studies have indicated that MBZ might modulate cancer cell migration through the S1P/FAK/vimentin pathway.161”
From Drug repurposing for cancer therapy (2024) · cites this paper as [161]
Mebendazole inhibits tumor growth via the JAK2/STAT3/Bcl-2 signaling pathway.
“MBZ has also been shown to inhibit tumor growth via the JAK2/STAT3/Bcl-2 signaling pathway”
From Drug repurposing for cancer therapy (2024) · cites this paper as [161]
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“161 MBZ has also been found to restrict the migratory and invasive tendencies of glioblastoma cells, and concurrently modulate pivotal markers in the EMT, suggesting a potential role for MBZ in mitigating glioblastoma metastasis.”
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- Authors
- Limbu, K. R., Chhetri, R. B., Oh, Y. S., Baek, D. J., & Park, E.-Y.
- Affiliations
- Mokpo National University (KR)
- Eulji University (KR)
- Corresponding author
- Baek, Dong Jae
- Park, Eun-Young
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2022-11-22
- Volume
- 27
- Issue
- 23
- Pages
- 8127
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC9739667
- OpenAlex
- W4310038672
- Cited by
- 12
- References
- 64
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 2
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (2020R1A2C1012156 and 2020R1F1A1068316) ((2020R1A2C1012156 and 2020R1F1A1068316))
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- mebendazole, pancreatic ductal adenocarcinoma, sphingosine-1-phosphate, sphingosine kinase 1, SK2, tumor cell proliferation, cell migration, chemoresistance, focal adhesion kinase, vimentin, sphingolipids
- MeSH terms
- Humans, Lysophospholipids, Mebendazole, Pancreatic Neoplasms, Sphingosine, Phosphotransferases (Alcohol Group Acceptor), Cell Proliferation
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