Autophagy in MCF-7 cancer cells induced by copper complexes.
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 IC50using 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
IC50values 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.
Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Katarína
K
Koňariková
Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Georgios A
GA
Perdikaris
Institute of Medical Biology and Genetics, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Helena
H
Gbelcová
Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Lucia
L
Andrezálová
Institute of Chemical Technology, Department of Biochemistry and Microbiology, Faculty of Food Biochemical Technology, Technicka 5, 166 28, Prague, Czech Republic.
Martin
M
Švéda
Institute of Chemical Technology, Department of Biochemistry and Microbiology, Faculty of Food Biochemical Technology, Technicka 5, 166 28, Prague, Czech Republic.
Tomáš
T
Ruml
Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Lucia
L
Laubertová
Institute of Medical Biology and Genetics, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Soňa
S
Režnáková
Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic. Electronic address: ingrid.zitnanova@fmed.uniba.sk.
Ingrid
I
Žitňanová
D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D003300:Copper / Q000494:pharmacology / Q000633:toxicity*; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D012545:Schiff Bases / Q000494:pharmacology / Q000633:toxicity
D012545:Schiff Bases; D003300:Copper
Autophagy; Cancer cell lines; Cell death; Schiff base copper complexes