New chalcone derivative exhibits antiproliferative potential by inducing G2/M cell cycle arrest, mitochondrial-mediated apoptosis and modulation of MAPK signalling pathway
| Autor: | Jan Mojzis, Peter Takáč, Martina Pilátová, Martin Kello, Zuzana Kudličková, Peter Petik, Mária Vilková, Pavlina Slepcikova |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chalcone Cell cycle checkpoint DNA repair MAP Kinase Signaling System Poly ADP ribose polymerase Blotting Western Antineoplastic Agents Apoptosis Toxicology Real-Time Polymerase Chain Reaction 03 medical and health sciences chemistry.chemical_compound Inhibitory Concentration 50 0302 clinical medicine Chalcones Annexin Cell Line Tumor Humans Cell Proliferation Molecular Structure Cell growth Chemistry General Medicine Flow Cytometry Cell biology Mitochondria G2 Phase Cell Cycle Checkpoints 030104 developmental biology 030220 oncology & carcinogenesis Cancer cell Colonic Neoplasms |
| Zdroj: | Chemico-biological interactions. 292 |
| ISSN: | 1872-7786 |
| Popis: | In the present study, we investigated antiproliferative activity of seven newly synthesized chalcone derivatives. Among tested compounds, (2 E)-3-(acridin-9-yl)-1-(2,6-dimethoxyphenyl)prop-2-en-1-one (1C) was the most potent with IC50 = 4.1 μmol/L in human colorectal HCT116 cells and was selected for further studies. Inhibition of cell proliferation was associated with cell cycle arrest in G2/M phase and dysregulation of α, α1 and β5 tubulins. Moreover, 1C caused disruption of the mitochondrial membrane potential and increased number of cells with sub G0/G1 DNA content which is considered as marker of apoptosis. Apoptosis was confirmed by annexin V/PI and AO/PI staining. Furthermore, we found increased concentration of cytochrome c, Smac/Diablo and increased caspase-3 and caspase-9 activity, cleavage of PARP as well as activation of DNA repair mechanisms in 1C-treated HCT116 cancer cells. Moreover this chalcone derivative up-regulated proapoptotic Bax expression and down-regulated antiapoptotic Bcl-2 and Bcl-xL expression. Additionally, 1C treatment led to modulation of MAPKs and Akt signalling pathways. In conclusion, our data showed ability of 1C to suppress cancel cell growth and provide the rationale for further in vivo study. |
| Databáze: | OpenAIRE |
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