Katarína Koňariková1, Georgios A Perdikaris1, Helena Gbelcová2, Lucia Andrezálová1, Martin Švéda3, Tomáš Ruml3, Lucia Laubertová1, Soňa Režnáková2, Ingrid Žitňanová4. 1. Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic. 2. Institute of Medical Biology and Genetics, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic. 3. Institute of Chemical Technology, Department of Biochemistry and Microbiology, Faculty of Food Biochemical Technology, Technicka 5, 166 28, Prague, Czech Republic. 4. Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic. Electronic address: ingrid.zitnanova@fmed.uniba.sk.
Abstract
BACKGROUND: Autophagy plays an important role in cancer cells. Targeting autophagy in cancer can provide new opportunities for drug development. METHODS: In this study we tested four Schiff base Cu(II) complexes against human breast cancer cells (MCF-7) and human non-cancerous cells (HEK-293T). We have tested their cytotoxic effect by evaluating IC50 using MTT test. To detect morphological changes of the actin fibers we have used fluorescent microscopy. To determine the type of cell death we used electrophoretic analysis and western blot analysis (protein LC3). RESULTS: IC50 values of the complexes increased with time of their influence, indicating acquired resistance of MCF-7 to the complexes. Healthy cells HEK-293T were not sensitive to the Cu(II) complexes. Compared with the control cells (cells without Cu(II) complexes) which were without morphological changes of actin fibers, Cu(II) complexes induced condensation and asymmetric conformational changes in actin filaments. To examine the type of cell death induced by the Cu(II) complexes we treated MCF-7 cells with Cu(II) complexes (1, 10, 50 and 100μmol/L) during a 72h incubation period. By electrophoresis we have not detected any DNA fragmentation. To determine whether Cu(II) complexes induced autophagy or necrotic cell death we used the western blot analysis. MCF-7 cells influenced with tested Cu(II) complexes produced LC3 protein after their 72h incubation indicating autophagy in MCF-7 cancer cells. CONCLUSIONS: Tested Schiff base copper (II) complexes have antiproliferative activity against cancer cells but not against healthy cells. They have induced autophagy in the cancer cell line MCF-7.
BACKGROUND: Autophagy plays an important role in cancer cells. Targeting autophagy in cancer can provide new opportunities for drug development. METHODS: In this study we tested four Schiff baseCu(II) complexes against humanbreast cancer cells (MCF-7) and human non-cancerous cells (HEK-293T). We have tested their cytotoxic effect by evaluating IC50 using MTT test. To detect morphological changes of the actin fibers we have used fluorescent microscopy. To determine the type of cell death we used electrophoretic analysis and western blot analysis (protein LC3). RESULTS: IC50 values of the complexes increased with time of their influence, indicating acquired resistance of MCF-7 to the complexes. Healthy cells HEK-293T were not sensitive to the Cu(II) complexes. Compared with the control cells (cells without Cu(II) complexes) which were without morphological changes of actin fibers, Cu(II) complexes induced condensation and asymmetric conformational changes in actin filaments. To examine the type of cell death induced by the Cu(II) complexes we treated MCF-7 cells with Cu(II) complexes (1, 10, 50 and 100μmol/L) during a 72h incubation period. By electrophoresis we have not detected any DNA fragmentation. To determine whether Cu(II) complexes induced autophagy or necrotic cell death we used the western blot analysis. MCF-7 cells influenced with tested Cu(II) complexes produced LC3 protein after their 72h incubation indicating autophagy in MCF-7 cancer cells. CONCLUSIONS: Tested Schiff basecopper (II) complexes have antiproliferative activity against cancer cells but not against healthy cells. They have induced autophagy in the cancer cell line MCF-7.
Authors: Yan Xia; Xingkai Liu; Luping Zhang; Jinzhu Zhang; Chaoying Li; Nan Zhang; Hong Xu; Yan Li Journal: Cancer Cell Int Date: 2019-04-03 Impact factor: 5.722