ArticlePharmacological reports : PR2023
Cytotoxic pathways activated by multifunctional thiosemicarbazones targeting sigma-2 receptors in breast and lung carcinoma cells.
Article in Pharmacological reports : PR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- Synthesis, characterization, crystal structures, antitumor activity, and computational study of novel thiosemicarbazone derivatives from thiazol-2/5-carbaldehyde.RSC advances · 2026Article
- Novel bakuchiol derivatives inhibit the migration and invasion of non-small cell lung cancer by suppressing epithelial-to-mesenchymal transition.RSC advances · 2025Article
- Recent Advances in the Development of Sigma Receptor (Radio)Ligands and Their Application in Tumors.ACS pharmacology & translational science · 2025Review
- Exploring Selenium-Functionalized Hydroxyapatite Using Organic Selenocystine for Antitumor Applications.Materials (Basel, Switzerland) · 2025Article
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Authors and funding
9 authors at 3 institutions in 1 country.
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Abstract
backgroundMultifunctional thiosemicarbazones (TSCs) able to bind sigma receptors and chelate metals are considered as a promising avenue for the treatment of pancreatic cancer due to the encouraging results obtained on in vitro and in vivo models. Here, we assessed the biochemical mechanism of these TSCs also on lung (A549) and breast (MCF7) cancer cells.
methodsThe density of sigma-2 receptors in normal (BEAS-2B and MCF10A) and in lung and breast (A549 and MCF7) cancer cells was evaluated by flow cytometry. In these cells, cytotoxicity (MTT assay) and activation of ER- and mitochondria-dependent cell death pathways (by spectrofluorimetric assays to measure Caspases 3/7/9; qRT-PCR detection of GRP78, ATF6, IRE1, PERK; MitoSOX, DCFDA-AM and JC-1 staining), induced by the TSCs FA4, MLP44, PS3 and ACThio1, were evaluated.
resultsFA4 and PS3 exerted more potent cytotoxicity than MLP44 and ACThio1 in all cancer cell lines, where the density of sigma-2 receptors was higher than in normal cells. Remarkably, FA4 promoted ER- and mitochondria-dependent cell death pathways in both cell models, whereas the other TSCs had variable, cell-dependent effects on the activation of the two proapoptotic pathways.
conclusionsOur data suggest that FA4 is a promising compound that deserves to be further studied for lung and breast cancer treatment. However, the other multifunctional TSCs also hold promise for the development of therapies towards a personalized medicine approach. Indeed, the presence of the sigma-2 receptor-targeting moiety would lead to a more specific tumor delivery embracing the characteristics of individual tumor types.
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