Novel Gold and Silver Carbene Complexes Exert Antitumor Effects Triggering the Reactive Oxygen Species Dependent Intrinsic Apoptotic Pathway
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- Domenico Iacopetta
- Department of Pharmacy, Health and Nutritional Sciences University of Calabria Via Pietro Bucci 87036 Arcavacata di Rende Italy
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- Annaluisa Mariconda
- Department of Biology and Chemistry University of Salerno Via Giovanni Paolo II, 132 Fisciano 84084 Italy
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- Carmela Saturnino
- Department of Science University of Basilicata Viale dell'Ateneo Lucano 10 Potenza 85100 Italy
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- Anna Caruso
- Department of Pharmacy, Health and Nutritional Sciences University of Calabria Via Pietro Bucci 87036 Arcavacata di Rende Italy
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- Giuseppe Palma
- SSD Sperimentazione Animale, Istituto Nazionale Tumori IRCCS, “Fondazione G. Pascale” Via Mariano Semmola Napoli 80131 Italy
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- Jessica Ceramella
- Department of Pharmacy, Health and Nutritional Sciences University of Calabria Via Pietro Bucci 87036 Arcavacata di Rende Italy
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- Noemi Muià
- Department of Pharmacy, Health and Nutritional Sciences University of Calabria Via Pietro Bucci 87036 Arcavacata di Rende Italy
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- Mariarita Perri
- Department of Pharmacy, Health and Nutritional Sciences University of Calabria Via Pietro Bucci 87036 Arcavacata di Rende Italy
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- Maria Stefania Sinicropi
- Department of Pharmacy, Health and Nutritional Sciences University of Calabria Via Pietro Bucci 87036 Arcavacata di Rende Italy
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- Maria Cristina Caroleo
- Department of Pharmacy, Health and Nutritional Sciences University of Calabria Via Pietro Bucci 87036 Arcavacata di Rende Italy
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- Pasquale Longo
- Department of Biology and Chemistry University of Salerno Via Giovanni Paolo II, 132 Fisciano 84084 Italy
説明
<jats:title>Abstract</jats:title><jats:p>Cisplatin and other platinum‐based drugs are well‐known valid anticancer drugs. However, during chemotherapy, the presence of numerous side effects and the onset of frequent phenomena of resistance has pushed many research groups to devise new metal‐based compounds holding improved anticancer properties and fewer undesired effects. Amongst the variety of synthesized compounds, significant antiproliferative effects have been obtained by employing organometallic compounds, particularly those based on silver and gold. With this in mind, we synthesized four compounds, two silver complexes and two gold complexes, with good inhibitory effects on the in vitro proliferation of breast and ovarian cancer‐cell models. The antitumor activity of the most active compound, that is, Au<jats:bold>L4</jats:bold>, was found to be ninefold higher than that of cisplatin, and this compound induced dramatic morphological changes in HeLa cells. Au<jats:bold>L4</jats:bold> induced PARP‐1 cleavage, caspases 3/7 and 9 activation, mitochondria disruption, cytochrome c release in cancer‐cell cytoplasm, and the intracellular production of reactive oxygen species. Thus, Au<jats:bold>L4</jats:bold> treatment caused cancer‐cell death by the intrinsic apoptotic pathway, whereas no cytotoxic effects were recorded upon treating non‐tumor cell lines. The reported outcomes may be an important contribution to the expanding knowledge of medicinal bio‐organometallic chemistry and enlarge the available anticancer toolbox, offering improved features, such as higher activity and/or selectivity, and opening the way to new discoveries and applications.</jats:p>
収録刊行物
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- ChemMedChem
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ChemMedChem 12 (24), 2054-2065, 2017-12-06
Wiley