Tumor Biology

, Volume 35, Issue 10, pp 9967–9975 | Cite as

Benzylidenetetralones, cyclic chalcone analogues, induce cell cycle arrest and apoptosis in HCT116 colorectal cancer cells

  • David Drutovic
  • Martina Chripkova
  • Martina Pilatova
  • Peter Kruzliak
  • Pal Perjesi
  • Marek Sarissky
  • Monica Lupi
  • Giovanna Damia
  • Massimo Broggini
  • Jan Mojzis
Research Article


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.


Benzylidenetetralones Cyclic chalcone analogues Cell cycle arrest Apoptosis Colorectal cancer cells 



adenosine diphosphate


complementary DNA


threshold cycle


deoxyribonucleic acid


deoxyuridine triphosphate


fluorescein isothiocyanate


messenger RNA


polymerase chain reaction


quantitative reverse transcription PCR


ribonucleic acid


terminal deoxynucleotidyl transferase



This work was supported by SEPO-II (ITMS code: 26220120039) and European Regional Development Fund—Project FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123). We would like to thank Elisa Caiola and Laura Carrassa for technical support and Tom Billingham for his careful proof-reading of the manuscript.

Conflict of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • David Drutovic
    • 1
  • Martina Chripkova
    • 1
  • Martina Pilatova
    • 1
  • Peter Kruzliak
    • 2
  • Pal Perjesi
    • 3
  • Marek Sarissky
    • 1
  • Monica Lupi
    • 4
  • Giovanna Damia
    • 5
  • Massimo Broggini
    • 5
  • Jan Mojzis
    • 1
  1. 1.Department of Pharmacology, Faculty of MedicinePavol Jozef Šafárik University in KošiceKošiceSlovak Republic
  2. 2.International Clinical Research CenterSt. Anne’s University HospitalBrnoCzech Republic
  3. 3.Institute of Pharmaceutical Chemistry, Faculty of MedicineUniversity of PécsPécsHungary
  4. 4.Laboratory of Cancer Pharmacology, Department of OncologyIRCCS - Istituto di Ricerche Farmacologiche Mario NegriMilanItaly
  5. 5.Laboratory of Molecular Pharmacology, Department of OncologyIRCCS - Istituto di Ricerche Farmacologiche Mario NegriMilanItaly

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