Benzylidenetetralones, cyclic chalcone analogues, induce cell cycle arrest and apoptosis in HCT116 colorectal cancer cells
| Autor: | Pál Perjési, Jan Mojzis, David Drutovic, Martina Pilátová, Peter Kruzliak, Monica Lupi, Martina Chripkova, Giovanna Damia, Marek Sarissky, Massimo Broggini |
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| Rok vydání: | 2014 |
| Předmět: |
Chalcone
Cell cycle checkpoint DNA damage Poly ADP ribose polymerase Blotting Western Fluorescent Antibody Technique Antineoplastic Agents Apoptosis Biology Real-Time Polymerase Chain Reaction Benzylidene Compounds chemistry.chemical_compound Chalcones Downregulation and upregulation In Situ Nick-End Labeling Humans Cell Proliferation TUNEL assay General Medicine Cell Cycle Checkpoints Flow Cytometry HCT116 Cells Molecular biology Real-time polymerase chain reaction chemistry Colorectal Neoplasms |
| Zdroj: | Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 35(10) |
| ISSN: | 1423-0380 |
| Popis: | Colorectal cancer is the third most common cancer in the world, with 1.2 million new cancer cases annually. Chalcones are secondary metabolite precursors of flavonoids that exhibit diverse biological activities, including antioxidant and antitumor activities. The aim of this study was to investigate the antiproliferative effect of new synthetic chalcone derivatives on HCT116 cells. (E)-2-(2′,4′-dimethoxybenzylidene)-1-tetralone (Q705) was found to be the most active (IC50 = 3.44 ± 0.25 μM). Based on these results, this compound was chosen for further analysis of its biochemical and molecular mechanisms. Our results showed that Q705 inhibited the growth and clonogenicity of HCT116 cells. The results of a flow cytometric analyses suggested that this compound caused a significant cell cycle arrest in G2/M phase and increased the proportion of cells in the subG0/G1 phase, marker of apoptosis. Q705-induced apoptosis was confirmed by TdT-mediated dUTP nick end labelling (TUNEL) assay. Treatment of HCT116 cells with this chalcone significantly increased the caspase-3,-7 activity and resulted in cleavage of poly-ADP-ribose polymerase (PARP). Changes in the nuclear morphology such as chromatin condensation were also observed. These effects were associated with a decreased expression of bcl-xL and increased overall ratio of bax/bcl-xL mRNA levels. Immunofluorescence and qRT-PCR analysis revealed that Q705 induced H2AX histone modifications characteristic of DNA damage, disruption of microtubule organization and downregulation of tubulins. In summary, these results suggest that the cyclic chalcone analogue Q705 has potential as a new compound for colorectal cancer therapy. |
| Databáze: | OpenAIRE |
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