Martin Kello1, David Drutovic2, Martina Bago Pilatova1, Vierka Tischlerova1, Pal Perjesi3, Jan Mojzis4. 1. P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic. 2. P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic; Institute of Animal Physiology and Genetics AS CR, v.v.i., Libechov, Czech Republic. 3. Institute of Pharmaceutical Chemistry, Faculty of Medicine, University of Pecs, Pecs, Hungary. 4. P.J. Safarik University, Faculty of Medicine, Department of Pharmacology, Kosice, Slovak Republic. Electronic address: jan.mojzis@upjs.sk.
Abstract
AIMS: Chalcones, naturally occurring open-chain polyphenols abundant in plants, have demonstrated antiproliferative activity in several cancer cell lines. In the present study, the potential anticancer activity of two synthetic analogues named Ch1 and Ch2 in colon cancer cell line was investigated. MAIN METHODS: Antiproliferative activities of both synthetic analogues were assessed by Growth Inhibition Assay (MTT) and xCELLigence cell analysis. Apoptosis was assessed by annexin V/PI staining (early stage) or by DNA fragmentation (final stage). To study the cell death mechanism induced by tested substances, we assessed a series of assays including measurements of the caspase 3 activity, membrane mitochondrial potential (MMP) changes, reactive oxygen species (ROS) production by flow cytometry and expression of important apoptosis-related genes by realtime PCR. KEY FINDINGS: We found concentration and time-dependent cytotoxicity, inhibition of proliferation of Caco-2 cells after Ch1 and Ch2 treatment in parallel with G2/M phase cell cycle arrest and increased cell proportion in subG0/G1 population with annexin V positivity. We demonstrated that both Ch1 and Ch2 induced caspase-dependent cell death associated with increased ROS production, suppressed Bcl-2 and Bcl-xL and enhanced Bax expression. Treatment of Ch1 also suppressed α-, α1- and β5-tubulins, on the other hand Ch2 only suppressed α-tubulin expression. SIGNIFICANCE: Presented chalcones induce apoptosis by intrinsic pathways, and therefore may be an interesting strategy for cancer therapy.
AIMS: Chalcones, naturally occurring open-chain polyphenols abundant in plants, have demonstrated antiproliferative activity in several cancer cell lines. In the present study, the potential anticancer activity of two synthetic analogues named Ch1 and Ch2 in colon cancer cell line was investigated. MAIN METHODS: Antiproliferative activities of both synthetic analogues were assessed by Growth Inhibition Assay (MTT) and xCELLigence cell analysis. Apoptosis was assessed by annexin V/PI staining (early stage) or by DNA fragmentation (final stage). To study the cell death mechanism induced by tested substances, we assessed a series of assays including measurements of the caspase 3 activity, membrane mitochondrial potential (MMP) changes, reactive oxygen species (ROS) production by flow cytometry and expression of important apoptosis-related genes by realtime PCR. KEY FINDINGS: We found concentration and time-dependent cytotoxicity, inhibition of proliferation of Caco-2 cells after Ch1 and Ch2 treatment in parallel with G2/M phase cell cycle arrest and increased cell proportion in subG0/G1 population with annexin V positivity. We demonstrated that both Ch1 and Ch2 induced caspase-dependent cell death associated with increased ROS production, suppressed Bcl-2 and Bcl-xL and enhanced Bax expression. Treatment of Ch1 also suppressed α-, α1- and β5-tubulins, on the other hand Ch2 only suppressed α-tubulin expression. SIGNIFICANCE: Presented chalcones induce apoptosis by intrinsic pathways, and therefore may be an interesting strategy for cancer therapy.
Authors: Desirée Magalhães Dos Santos; Camila Valesca Jardim Rocha; Elita Ferreira da Silveira; Marcelo Augusto Germani Marinho; Marisa Raquel Rodrigues; Nichole Osti Silva; Ailton da Silva Ferreira; Neusa Fernandes de Moura; Gabriel Jorge Sagrera Darelli; Elizandra Braganhol; Ana Paula Horn; Vânia Rodrigues de Lima Journal: J Membr Biol Date: 2018-02-08 Impact factor: 1.843
Authors: Peter Takac; Martin Kello; Maria Vilkova; Janka Vaskova; Radka Michalkova; Gabriela Mojzisova; Jan Mojzis Journal: Biomolecules Date: 2020-02-22
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