Chalcone-Acridine Hybrid Suppresses Melanoma Cell Progression via G2/M Cell Cycle Arrest, DNA Damage, Apoptosis, and Modulation of MAP Kinases Activity
| Autor: | Maria Gazdova, Radka Michalkova, Martin Kello, Maria Vilkova, Zuzana Kudlickova, Janette Baloghova, Ladislav Mirossay, Jan Mojzis |
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| Rok vydání: | 2022 |
| Předmět: |
Caspase 3
Organic Chemistry Cytochromes c Apoptosis Cell Cycle Proteins Cell Cycle Checkpoints General Medicine Catalysis Computer Science Applications G2 Phase Cell Cycle Checkpoints Inorganic Chemistry Chalcone Chalcones Cell Line Tumor Humans Acridines Cyclin B1 Phosphorylation Physical and Theoretical Chemistry Melanoma Molecular Biology Spectroscopy bcl-2-Associated X Protein DNA Damage chalcone-acridine hybrid apoptosis cell cycle arrest DNA damage MAP kinases |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 20; Pages: 12266 Radka Michalková |
| ISSN: | 1422-0067 |
| Popis: | This study was focused on investigating the antiproliferative effects of chalcone hybrids in melanoma cancer cells. Among seven chalcone hybrids, the chalcone-acridine hybrid 1C was the most potent and was selected for further antiproliferative mechanism studies. This in vitro study revealed the potent antiproliferative effect of 1C via cell cycle arrest and apoptosis induction. Cell cycle arrest at the G2/M phase was associated with modulation of expression or phosphorylation of specific cell cycle-associated proteins (cyclin B1, p21, and ChK1), tubulins, as well as with the activation of the DNA damage response pathway. Chalcone 1C also induced apoptosis accompanied by mitochondrial dysfunction evidenced by a decrease in mitochondrial membrane potential, increase in Bax/Bcl-xL ratio and cytochrome c release followed by caspase 3/7 activation. In addition, increased phosphorylation of MAP kinases (Erk1/2, p38 and JNK) was observed in chalcone 1C-treated melanoma cells. The strong antiproliferative activities of this chalcone-acridine hybrid suggest that it may be useful as an antimelanoma agent in humans. |
| Databáze: | OpenAIRE |
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