4.5 Article

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

Journal

FUTURE MEDICINAL CHEMISTRY
Volume 12, Issue 10, Pages 897-914

Publisher

Newlands Press Ltd
DOI: 10.4155/fmc-2019-0215

Keywords

apoptosis; breast cancer; cell cycle; Zn(S-pr-thiosal)(2) complex

Funding

  1. Ministry of Education, Science and Technological Development, Serbia [ON 175069, ON 175071]
  2. bilateral project with PR China [06/2018]
  3. Faculty of Medical Sciences of the University of Kragujevac, Serbia [MP 02/14, JP 10/18]
  4. Ministry of Education, Science, Research and Sport of the Slovak Republic (project VEGA ) [1/0148/19]
  5. Operation program Prague Competitiveness [CZ.2.16/3.1.00/24510]

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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.

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