Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma Cells
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fourth cause of cancer-related deaths worldwide. Presently, a few drugs are available for HCC treatment and prevention, including both natural and synthetic compounds. In this study, a new chalcone, (<i>E</i>)...
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| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/12/3120 |
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| author | Anna Santarsiero Ilaria Pappalardo Gabriella Margherita Rosa Isabella Pisano Stefano Superchi Paolo Convertini Simona Todisco Patrizia Scafato Vittoria Infantino |
| author_facet | Anna Santarsiero Ilaria Pappalardo Gabriella Margherita Rosa Isabella Pisano Stefano Superchi Paolo Convertini Simona Todisco Patrizia Scafato Vittoria Infantino |
| author_sort | Anna Santarsiero |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fourth cause of cancer-related deaths worldwide. Presently, a few drugs are available for HCC treatment and prevention, including both natural and synthetic compounds. In this study, a new chalcone, (<i>E</i>)-1-(2,4,6-triethoxyphenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (ETTC), was synthesized and its effects and mechanisms of action over human hepatoma cells were investigated. Cytotoxic activity was revealed in HCC cells, while no effects were observed in normal hepatocytes. In HCC cells, ETTC caused subG1 cell cycle arrest and apoptosis, characterized by nuclear fragmentation. The activation of caspases 3/7 and 9, the increase in pro-apoptotic BAX, and the decrease in anti-apoptotic BCL-2 suggest the activation of the intrinsic pathway of apoptosis. ETTC mitochondrial targeting is confirmed by the reduction in mitochondrial membrane potential and Complex I activity together with levels of superoxide anion increasing. Our outcomes prove the potential mitochondria-mediated antitumor effect of newly synthesized chalcone ETTC in HCC. |
| first_indexed | 2024-03-09T17:18:04Z |
| format | Article |
| id | doaj.art-3f64c9a469db4102907830f7c19aa085 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T17:18:04Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-3f64c9a469db4102907830f7c19aa0852023-11-24T13:27:10ZengMDPI AGBiomedicines2227-90592022-12-011012312010.3390/biomedicines10123120Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma CellsAnna Santarsiero0Ilaria Pappalardo1Gabriella Margherita Rosa2Isabella Pisano3Stefano Superchi4Paolo Convertini5Simona Todisco6Patrizia Scafato7Vittoria Infantino8Department of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, 70125 Bari, ItalyDepartment of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyDepartment of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, ItalyHepatocellular carcinoma (HCC) is the most common type of liver cancer and the fourth cause of cancer-related deaths worldwide. Presently, a few drugs are available for HCC treatment and prevention, including both natural and synthetic compounds. In this study, a new chalcone, (<i>E</i>)-1-(2,4,6-triethoxyphenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (ETTC), was synthesized and its effects and mechanisms of action over human hepatoma cells were investigated. Cytotoxic activity was revealed in HCC cells, while no effects were observed in normal hepatocytes. In HCC cells, ETTC caused subG1 cell cycle arrest and apoptosis, characterized by nuclear fragmentation. The activation of caspases 3/7 and 9, the increase in pro-apoptotic BAX, and the decrease in anti-apoptotic BCL-2 suggest the activation of the intrinsic pathway of apoptosis. ETTC mitochondrial targeting is confirmed by the reduction in mitochondrial membrane potential and Complex I activity together with levels of superoxide anion increasing. Our outcomes prove the potential mitochondria-mediated antitumor effect of newly synthesized chalcone ETTC in HCC.https://www.mdpi.com/2227-9059/10/12/3120chalconehepatocellular carcinoma (HCC)intrinsic pathway of apoptosismitochondriaBAXBCL-2 |
| spellingShingle | Anna Santarsiero Ilaria Pappalardo Gabriella Margherita Rosa Isabella Pisano Stefano Superchi Paolo Convertini Simona Todisco Patrizia Scafato Vittoria Infantino Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma Cells Biomedicines chalcone hepatocellular carcinoma (HCC) intrinsic pathway of apoptosis mitochondria BAX BCL-2 |
| title | Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma Cells |
| title_full | Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma Cells |
| title_fullStr | Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma Cells |
| title_full_unstemmed | Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma Cells |
| title_short | Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma Cells |
| title_sort | mitochondrial role in intrinsic apoptosis induced by a new synthesized chalcone in hepatocellular carcinoma cells |
| topic | chalcone hepatocellular carcinoma (HCC) intrinsic pathway of apoptosis mitochondria BAX BCL-2 |
| url | https://www.mdpi.com/2227-9059/10/12/3120 |
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