Research Article

The Zn(S-pr-thiosal)₂ complex attenuates murine breast cancer growth by inducing apoptosis and G1/S cell cycle arrest

Department of Transfusiology, Pula General Hospital, Pula, 52100, Croatia

Department of Cytology, Pula General Hospital, Pula, 52100, Croatia

Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia

Department of Otorhinolaryngology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 34000, Serbia

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Milena Jurisevic

Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia

Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 34000, Serbia

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Jelena Milovanovic

Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia

Department of Histology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 34000, Serbia

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Marina Mijajlovic

Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 34000, Serbia

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Milos Nikolic

Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 34000, Serbia

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Tatjana Kanjevac

**Author for correspondence: Tel.: +38134 306 800;

E-mail Address: tatjanakanjevac@yahoo.com

Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 34000, Serbia

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Ivan Potočňák

Institute of Chemistry, Faculty of Science, P.J. Šafárik University in Košice, Košice, 34000, Slovakia

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Erika Samoľová

Institute of Chemistry, Faculty of Science, P.J. Šafárik University in Košice, Košice, 34000, Slovakia

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Zoran R Ratkovic

Department of Chemistry, Faculty of Science, University of Kragujevac, Kragujevac, 34000, Serbia

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Gordana Radic

Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 34000, Serbia

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Marija Milovanovic

Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia

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Jelena Pantic

Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia

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Nebojsa Arsenijevic

Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia

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Gordana D Radosavljevic

*Author for correspondence: Tel.: +38134 306 800;

E-mail Address: perun.gr@gmail.com

Center for Molecular Medicine & Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia

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Published Online:8 Apr 2020https://doi.org/10.4155/fmc-2019-0215

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Abstract

Aim: We investigated the antitumor effects of zinc(II) complex with S-propyl thiosalicylic acid [Zn(S-pr-thiosal)₂] in 4T1 murine breast cancer model. Results: The Zn(S-pr-thiosal)₂ complex reduced primary tumor growth in vivo and induced tumor cell apoptosis. The Zn(S-pr-thiosal)₂ complex disrupted the balance between pro- and antiapoptotic Bcl-2 family members in 4T1 cells and induced G1/S cell cycle arrest. The Zn(S-pr-thiosal)₂ complex increased the percentage of p16, p21 and p27 positive 4T1 cells. There was a significantly decrease in expression of STAT3 and its targets c-Myc and cyclin D3 in 4T1 cells treated with the Zn(S-pr-thiosal)₂ complex thus contributing to G1/S cell cycle arrest and/or apoptosis. Conclusion: Our data suggest that the Zn(S-pr-thiosal)₂ complex restricted tumor growth through induction of mitochondrial-driven apoptosis and suppression of cell cycle progression.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 12, No. 10

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History

Received 23 July 2019

Accepted 26 February 2020

Published online 8 April 2020

Published in print May 2020

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Keywords

Acknowledgments

The authors thank A Ilic and D Tomasevic for excellent technical assistance.

Financial & competing interests disclosure

This work was funded by grants from the Ministry of Education, Science and Technological Development, Serbia (ON 175069 and ON 175071), the bilateral project with PR China (06/2018), and the Faculty of Medical Sciences of the University of Kragujevac, Serbia (MP 02/14 and JP 10/18). This work was further supported by the Ministry of Education, Science, Research and Sport of the Slovak Republic (project VEGA no. 1/0148/19). The crystallographic measurements used instruments of the ASTRA lab established within the Operation program Prague Competitiveness-project CZ.2.16/3.1.00/24510. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All experiments were approved by and conducted in accordance with the Guidelines of the Animal Ethics Committee of the Faculty of Medical Sciences of the University of Kragujevac, Serbia.

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The Zn(S-pr-thiosal)2 complex attenuates murine breast cancer growth by inducing apoptosis and G1/S cell cycle arrest

Abstract

References

The Zn(S-pr-thiosal)₂ complex attenuates murine breast cancer growth by inducing apoptosis and G1/S cell cycle arrest