Combination of Heme Oxygenase-1 Inhibition and Sigma Receptor Modulation for Anticancer Activity
Cancer is a multifactorial disease that may be tackled by targeting different signaling pathways. Heme oxygenase-1 (HO-1) and sigma receptors (σRs) are both overexpressed in different human cancers, including prostate and brain, contributing to the cancer spreading. In the present study, we investig...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/13/3860 |
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| author | Giuseppe Romeo Valeria Ciaffaglione Emanuele Amata Maria Dichiara Loredana Calabrese Luca Vanella Valeria Sorrenti Salvo Grosso Agata Grazia D’Amico Velia D’Agata Sebastiano Intagliata Loredana Salerno |
| author_facet | Giuseppe Romeo Valeria Ciaffaglione Emanuele Amata Maria Dichiara Loredana Calabrese Luca Vanella Valeria Sorrenti Salvo Grosso Agata Grazia D’Amico Velia D’Agata Sebastiano Intagliata Loredana Salerno |
| author_sort | Giuseppe Romeo |
| collection | DOAJ |
| description | Cancer is a multifactorial disease that may be tackled by targeting different signaling pathways. Heme oxygenase-1 (HO-1) and sigma receptors (σRs) are both overexpressed in different human cancers, including prostate and brain, contributing to the cancer spreading. In the present study, we investigated whether HO-1 inhibitors and σR ligands, as well a combination of the two, may influence DU145 human prostate and U87MG human glioblastoma cancer cells proliferation. In addition, we synthesized, characterized, and tested a small series of novel hybrid compounds (HO-1/σRs) <b>1</b>–<b>4</b> containing the chemical features needed for HO-1 inhibition and σR modulation. Herein, we report for the first time that targeting simultaneously HO-1 and σR proteins may be a good strategy to achieve increased antiproliferative activity against DU145 and U87MG cells, with respect to the mono administration of the parent compounds. The obtained outcomes provide an initial proof of concept useful to further optimize the structure of HO-1/σRs hybrids to develop novel potential anticancer agents. |
| first_indexed | 2024-03-10T10:05:53Z |
| format | Article |
| id | doaj.art-c7c17f4ae8db4615a7d882c9978e04ba |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:05:53Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c7c17f4ae8db4615a7d882c9978e04ba2023-11-22T01:35:56ZengMDPI AGMolecules1420-30492021-06-012613386010.3390/molecules26133860Combination of Heme Oxygenase-1 Inhibition and Sigma Receptor Modulation for Anticancer ActivityGiuseppe Romeo0Valeria Ciaffaglione1Emanuele Amata2Maria Dichiara3Loredana Calabrese4Luca Vanella5Valeria Sorrenti6Salvo Grosso7Agata Grazia D’Amico8Velia D’Agata9Sebastiano Intagliata10Loredana Salerno11Department of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, University of Catania, 95100 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug and Health Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyCancer is a multifactorial disease that may be tackled by targeting different signaling pathways. Heme oxygenase-1 (HO-1) and sigma receptors (σRs) are both overexpressed in different human cancers, including prostate and brain, contributing to the cancer spreading. In the present study, we investigated whether HO-1 inhibitors and σR ligands, as well a combination of the two, may influence DU145 human prostate and U87MG human glioblastoma cancer cells proliferation. In addition, we synthesized, characterized, and tested a small series of novel hybrid compounds (HO-1/σRs) <b>1</b>–<b>4</b> containing the chemical features needed for HO-1 inhibition and σR modulation. Herein, we report for the first time that targeting simultaneously HO-1 and σR proteins may be a good strategy to achieve increased antiproliferative activity against DU145 and U87MG cells, with respect to the mono administration of the parent compounds. The obtained outcomes provide an initial proof of concept useful to further optimize the structure of HO-1/σRs hybrids to develop novel potential anticancer agents.https://www.mdpi.com/1420-3049/26/13/3860heme oxygenaseHO-1 inhibitorssigma receptorsσR ligandsDU145anticancer activity |
| spellingShingle | Giuseppe Romeo Valeria Ciaffaglione Emanuele Amata Maria Dichiara Loredana Calabrese Luca Vanella Valeria Sorrenti Salvo Grosso Agata Grazia D’Amico Velia D’Agata Sebastiano Intagliata Loredana Salerno Combination of Heme Oxygenase-1 Inhibition and Sigma Receptor Modulation for Anticancer Activity Molecules heme oxygenase HO-1 inhibitors sigma receptors σR ligands DU145 anticancer activity |
| title | Combination of Heme Oxygenase-1 Inhibition and Sigma Receptor Modulation for Anticancer Activity |
| title_full | Combination of Heme Oxygenase-1 Inhibition and Sigma Receptor Modulation for Anticancer Activity |
| title_fullStr | Combination of Heme Oxygenase-1 Inhibition and Sigma Receptor Modulation for Anticancer Activity |
| title_full_unstemmed | Combination of Heme Oxygenase-1 Inhibition and Sigma Receptor Modulation for Anticancer Activity |
| title_short | Combination of Heme Oxygenase-1 Inhibition and Sigma Receptor Modulation for Anticancer Activity |
| title_sort | combination of heme oxygenase 1 inhibition and sigma receptor modulation for anticancer activity |
| topic | heme oxygenase HO-1 inhibitors sigma receptors σR ligands DU145 anticancer activity |
| url | https://www.mdpi.com/1420-3049/26/13/3860 |
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