Related Experiment Video
Updated: Sep 21, 2025
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
A Drug Screening Revealed Novel Potential Agents against Malignant Pleural Mesothelioma
Irene Dell'Anno1, Alessandra Melani1, Sarah A Martin2
1Genetic Unit, Department of Biology, University of Pisa, 56126 Pisa, Italy.
Abstract:
The lack of effective therapies remains one of the main challenges for malignant pleural mesothelioma (MPM). In this perspective, drug repositioning could accelerate the identification of novel treatments. We screened 1170 FDA-approved drugs on a SV40-immortalized mesothelial (MeT-5A) and five MPM (Mero-14, Mero-25, IST-Mes2, NCI-H28 and MSTO-211H) cell lines. Biological assays were carried out for 41 drugs, showing the highest cytotoxicity and for whom there were a complete lack of published literature in MPM. Cytotoxicity and caspase activation were evaluated with commercially available kits and cell proliferation was assayed using MTT assay and by clonogenic activity with standard protocols. Moreover, the five most effective drugs were further evaluated on patient-derived primary MPM cell lines. The most active molecules were cephalomannine, ouabain, alexidine, thonzonium bromide, and emetine. Except for alexidine, these drugs inhibited the clonogenic ability and caspase activation in all cancer lines tested. The proliferation was inhibited also on an extended panel of cell lines, including primary MPM cells. Thus, we suggest that cephalomannine, ouabain, thonzonium bromide, and emetine could represent novel candidates to be repurposed for improving the arsenal of therapeutic weapons in the fight against MPM.
Insights
Drug repositioning identified four potential new therapies for malignant pleural mesothelioma (MPM). Cephalomannine, ouabain, thonzonium bromide, and emetine show promise in preclinical models for this challenging cancer.
Area of Science:
- Oncology
- Pharmacology
- Drug Discovery
Background:
- Malignant pleural mesothelioma (MPM) lacks effective treatments, necessitating novel therapeutic strategies.
- Drug repositioning offers a faster route to identifying new cancer therapies by repurposing existing drugs.
Purpose of the Study:
- To screen FDA-approved drugs for potential repurposing against malignant pleural mesothelioma.
- To identify novel drug candidates that inhibit MPM cell proliferation and viability.
Main Methods:
- Screened 1170 FDA-approved drugs on MPM cell lines.
- Evaluated cytotoxicity, caspase activation, and cell proliferation (MTT, clonogenic assays).
- Tested top drug candidates on patient-derived primary MPM cells.
Main Results:
- Identified cephalomannine, ouabain, alexidine, thonzonium bromide, and emetine as cytotoxic to MPM cells.
- Cephalomannine, ouabain, thonzonium bromide, and emetine inhibited clonogenic ability and caspase activation.
- These four drugs demonstrated proliferation inhibition in various MPM cell lines, including primary cells.
Conclusions:
- Cephalomannine, ouabain, thonzonium bromide, and emetine are promising candidates for MPM drug repurposing.
- These drugs could enhance therapeutic options for malignant pleural mesothelioma.
- Further investigation is warranted to explore their clinical efficacy in MPM treatment.
