Agnieszka Marczak1, Marta Denel-Bobrowska1, Małgorzata Łukawska2, Irena Oszczapowicz3. 1. Department of Thermobiology, Institute of Biophysics, Faculty of Biology and Environmental Protection, Lodz University Pomorska, Lodz, Poland. 2. Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, Warsaw, Poland lukawskam@iba.waw.pl. 3. Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, Warsaw, Poland.
Abstract
BACKGROUND/AIM: The ability of five formamidinodoxorubicins to induce apoptosis of MCF-7 breast cancer cells was tested. All these compounds were modified at C-3' and contain a formamidine group (-N=CH-NRR), with the rest of the cyclic secondary amine (HNRR) of a gradually increasing ring size. MATERIALS AND METHODS: Cytotoxicity was assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To analyze apoptosis, double staining using fluorescence probes Hoechst 33258/propidium iodide (PI) and annexin V- Fluorescein isothiocyanate/PI was carried-out. Additionally, the TdT-mediated dUTP nick-end labelling test and activity of caspase 3 were determined. RESULTS: The four tested derivatives displayed a significant increase in antiproliferative activity in comparison to doxorubicin. All of the tested derivatives induced caspase-dependent apoptosis of MCF-7 cells. CONCLUSION: DOX-F MOR and DOX-F PAZ analogs are more potent apoptosis inducers than doxorubicin. Copyright
BACKGROUND/AIM: The ability of five formamidinodoxorubicins to induce apoptosis of MCF-7 breast cancer cells was tested. All these compounds were modified at C-3' and contain a formamidine group (-N=CH-NRR), with the rest of the cyclic secondary amine (HNRR) of a gradually increasing ring size. MATERIALS AND METHODS:Cytotoxicity was assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. To analyze apoptosis, double staining using fluorescence probes Hoechst 33258/propidium iodide (PI) and annexin V- Fluorescein isothiocyanate/PI was carried-out. Additionally, the TdT-mediated dUTP nick-end labelling test and activity of caspase 3 were determined. RESULTS: The four tested derivatives displayed a significant increase in antiproliferative activity in comparison to doxorubicin. All of the tested derivatives induced caspase-dependent apoptosis of MCF-7 cells. CONCLUSION:DOX-F MOR and DOX-F PAZ analogs are more potent apoptosis inducers than doxorubicin. Copyright
Authors: Andrey E Shchekotikhin; Lyubov G Dezhenkova; Vladimir B Tsvetkov; Yuri N Luzikov; Yulia L Volodina; Victor V Tatarskiy; Anastasia A Kalinina; Michael I Treshalin; Helen M Treshalina; Vladimir I Romanenko; Dmitry N Kaluzhny; Michael Kubbutat; Dominique Schols; Yves Pommier; Alexander A Shtil; Maria N Preobrazhenskaya Journal: Eur J Med Chem Date: 2016-02-04 Impact factor: 6.514