Cytotoxic and genotoxic effect of copper complexes on human colon carcinoma and mouse embryonic fibroblast cell lines.

Lucia Laubertová¹, Katarína Koňariková², Lucia Andrezálová³, Helena Gbelcová⁴, Ľubomír Danišovič⁵, Daniel Böhmer⁶, Ingrid Žitňanová⁷, Zdeňka Ďuračková⁸

1 Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University, Faculty of Medicine, Sasinkova 2, 813 72, Bratislava, Slovak Republic

2 Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University, Faculty of Medicine, Sasinkova 2, 813 72, Bratislava, Slovak Republic

3 Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University, Faculty of Medicine, Sasinkova 2, 813 72, Bratislava, Slovak Republic

4 Institute of Medical Biology and Genetics, Comenius University in Bratislava, Faculty of Medicine Sasinkova 4, 813 72 Bratislava, Slovak Republic

5 Institute of Medical Biology and Genetics, Comenius University in Bratislava, Faculty of Medicine Sasinkova 4, 813 72 Bratislava, Slovak Republic

6 Institute of Medical Biology and Genetics, Comenius University in Bratislava, Faculty of Medicine Sasinkova 4, 813 72 Bratislava, Slovak Republic

7 Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University, Faculty of Medicine, Sasinkova 2, 813 72, Bratislava, Slovak Republic

8 Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University, Faculty of Medicine, Sasinkova 2, 813 72, Bratislava, Slovak Republic

Abstract

The fundamental role of copper and the recognition of its complexes as important bioactive compounds in vitro and in vivo aroused an ever-increasing interest in these agents as potential drugs for therapeutic intervention in various diseases. Current interest in Cu-complexes is stemming from their potential use as antimicrobial, antiviral, anti-inflammatory, antitumor agents, enzyme inhibitors or chemical nucleases. [1]

This study investigated cytotoxic and genotoxic effects of two copper complexes MK3 (trans-bis(ethanol)tetrakis(imidazole)Cu(II)(2+)bis[µ-(N-salicylidene-D,L-glutamato-N,O)-κO:κO´-(imidazole)Cu(II)(2-)]) and MK5 ([Cu(N-salicylidene-D,L-glutamato)(2-methylimidazole]) in vitro. Human colon carcinoma cell line HT-29 and mouse embryonic fibroblast cell line NIH-3T3 served as experimental models. The effect of Cu-complexes on proliferation was monitored by direct cells counting. Genotoxic effect of Cu-complexes was monitored by single cell gel electrophoresis – SCGE.

Cytotoxic effect of Cu-complexes was depended on the concentration and time of influence.

The highest tested concentrations induced an immediate arrest of cell proliferation and/or partial degeneration of HT-29 and NIH-3T3 cells after 24 h influence.

Genotoxic effect of Cu-complexes was manifested by oxidative DNA damage. The level of direct DNA strand breaks was depended on the concentration of Cu-complex.

Acknowledgement: This project was supported by Rozum a zdravie.

References

[1] Iakovidis, I. et al. Copper and Its Complexes inMedicine: A Biochemical Approach. Molecular Biology International, Volume 2011 (2011): 13

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DOI^®: 10.3288/contoo.paper.1480