Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism Reprogramming
Improvement of anticancer treatments is associated with increased survival of cancer patients at risk of cardiac disease. Therefore, there is an urgent need for new therapeutic molecules capable of preventing acute and long-term cardiotoxicity. Here, using commercial and home-made chemolibraries, we...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/3/474 |
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| author | Dawei Liu Félix Peyre Yahir Alberto Loissell-Baltazar Delphine Courilleau Sandra Lacas-Gervais Valérie Nicolas Eric Jacquet Svetlana Dokudovskaya Frédéric Taran Jean-Christophe Cintrat Catherine Brenner |
| author_facet | Dawei Liu Félix Peyre Yahir Alberto Loissell-Baltazar Delphine Courilleau Sandra Lacas-Gervais Valérie Nicolas Eric Jacquet Svetlana Dokudovskaya Frédéric Taran Jean-Christophe Cintrat Catherine Brenner |
| author_sort | Dawei Liu |
| collection | DOAJ |
| description | Improvement of anticancer treatments is associated with increased survival of cancer patients at risk of cardiac disease. Therefore, there is an urgent need for new therapeutic molecules capable of preventing acute and long-term cardiotoxicity. Here, using commercial and home-made chemolibraries, we performed a robust phenotypic high-throughput screening in rat cardiomyoblast cell line H9c2, searching for small molecules capable of inhibiting cell death. A screen of 1600 compounds identified six molecules effective in preventing necrosis and apoptosis induced by H<sub>2</sub>O<sub>2</sub> and camptothecin in H9c2 cells and in rat neonatal ventricular myocytes. In cells treated with these molecules, we systematically evaluated the expression of BCL-2 family members, autophagy progression, mitochondrial network structure, regulation of mitochondrial fusion/fission, reactive oxygen species, and ATP production. We found that these compounds affect autophagy induction to prevent cardiac cell death and can be promising cardioprotective drugs during chemotherapy. |
| first_indexed | 2024-03-10T00:03:20Z |
| format | Article |
| id | doaj.art-81e185c893984ddf9d0fd96e88019aa0 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T00:03:20Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-81e185c893984ddf9d0fd96e88019aa02023-11-23T16:12:33ZengMDPI AGCells2073-44092022-01-0111347410.3390/cells11030474Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism ReprogrammingDawei Liu0Félix Peyre1Yahir Alberto Loissell-Baltazar2Delphine Courilleau3Sandra Lacas-Gervais4Valérie Nicolas5Eric Jacquet6Svetlana Dokudovskaya7Frédéric Taran8Jean-Christophe Cintrat9Catherine Brenner10Centre National de Recherche Scientifique (CNRS), Institut Gustave Roussy, Aspects Métaboliques et Systémiques de l’Oncogénèse pour de Nouvelles Approches Thérapeutiques, Université Paris-Saclay, 94805 Villejuif, FranceCentre National de Recherche Scientifique (CNRS), Institut Gustave Roussy, Aspects Métaboliques et Systémiques de l’Oncogénèse pour de Nouvelles Approches Thérapeutiques, Université Paris-Saclay, 94805 Villejuif, FranceCentre National de Recherche Scientifique (CNRS), Institut Gustave Roussy, Aspects Métaboliques et Systémiques de l’Oncogénèse pour de Nouvelles Approches Thérapeutiques, Université Paris-Saclay, 94805 Villejuif, FranceInserm, Centre National de Recherche Scientifique (CNRS), Ingénierie et Plateformes au Service de l’Innovation Thérapeutique, Université Paris-Saclay, 92296 Châtenay-Malabry, FranceCentre Commun de Microscopie Appliquée, CCMA, Université Côte d’Azur, 06103 Nice, FranceInserm, Centre National de Recherche Scientifique (CNRS), Ingénierie et Plateformes au Service de l’Innovation Thérapeutique, Université Paris-Saclay, 92296 Châtenay-Malabry, FranceInstitut de Chimie des Substances Naturelles, Université Paris-Saclay, CNRS, 91190 Gif-sur-Yvette, FranceCentre National de Recherche Scientifique (CNRS), Institut Gustave Roussy, Aspects Métaboliques et Systémiques de l’Oncogénèse pour de Nouvelles Approches Thérapeutiques, Université Paris-Saclay, 94805 Villejuif, FranceDépartement Médicaments et Technologies pour la Santé (DMTS), Université Paris Saclay, CEA, INRAE, SCBM, 91191 Gif-sur-Yvette, FranceDépartement Médicaments et Technologies pour la Santé (DMTS), Université Paris Saclay, CEA, INRAE, SCBM, 91191 Gif-sur-Yvette, FranceCentre National de Recherche Scientifique (CNRS), Institut Gustave Roussy, Aspects Métaboliques et Systémiques de l’Oncogénèse pour de Nouvelles Approches Thérapeutiques, Université Paris-Saclay, 94805 Villejuif, FranceImprovement of anticancer treatments is associated with increased survival of cancer patients at risk of cardiac disease. Therefore, there is an urgent need for new therapeutic molecules capable of preventing acute and long-term cardiotoxicity. Here, using commercial and home-made chemolibraries, we performed a robust phenotypic high-throughput screening in rat cardiomyoblast cell line H9c2, searching for small molecules capable of inhibiting cell death. A screen of 1600 compounds identified six molecules effective in preventing necrosis and apoptosis induced by H<sub>2</sub>O<sub>2</sub> and camptothecin in H9c2 cells and in rat neonatal ventricular myocytes. In cells treated with these molecules, we systematically evaluated the expression of BCL-2 family members, autophagy progression, mitochondrial network structure, regulation of mitochondrial fusion/fission, reactive oxygen species, and ATP production. We found that these compounds affect autophagy induction to prevent cardiac cell death and can be promising cardioprotective drugs during chemotherapy.https://www.mdpi.com/2073-4409/11/3/474apoptosisautophagycardioprotectioncardiotoxicitymitochondrionscreening |
| spellingShingle | Dawei Liu Félix Peyre Yahir Alberto Loissell-Baltazar Delphine Courilleau Sandra Lacas-Gervais Valérie Nicolas Eric Jacquet Svetlana Dokudovskaya Frédéric Taran Jean-Christophe Cintrat Catherine Brenner Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism Reprogramming Cells apoptosis autophagy cardioprotection cardiotoxicity mitochondrion screening |
| title | Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism Reprogramming |
| title_full | Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism Reprogramming |
| title_fullStr | Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism Reprogramming |
| title_full_unstemmed | Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism Reprogramming |
| title_short | Identification of Small Molecules Inhibiting Cardiomyocyte Necrosis and Apoptosis by Autophagy Induction and Metabolism Reprogramming |
| title_sort | identification of small molecules inhibiting cardiomyocyte necrosis and apoptosis by autophagy induction and metabolism reprogramming |
| topic | apoptosis autophagy cardioprotection cardiotoxicity mitochondrion screening |
| url | https://www.mdpi.com/2073-4409/11/3/474 |
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