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Pathology & Oncology Research

, Volume 23, Issue 2, pp 335–343 | Cite as

Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines

  • Mila Ljujic
  • Sanja Mijatovic
  • Mirna Z. Bulatovic
  • Marija Mojic
  • Danijela Maksimovic-Ivanic
  • Dragica Radojkovic
  • Aleksandra TopicEmail author
Original Article

Abstract

Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance.

Keywords

Alpha-1-antitrypsin Cisplatin Prostate cancer Melanoma cancer 

Notes

Acknowledgments

This work was supported by the Serbian Ministry of Education and Science (Grants No 173013 and 173008). Authors wish to thank Dr. Djordje Miljkovic from Institute for Biological Research “Sinisa Stankovic”, University of Belgrade for help in performing flow cytometry and Dr. Stanislava Stosic Grujicic from Institute for Biological Research “Sinisa Stankovic”, University of Belgrade for insightful comments and critical reading of the manuscript.

Compliance with Ethical Standards

Conflict of Interest

The authors have declared no conflicts of interest.

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Copyright information

© Arányi Lajos Foundation 2016

Authors and Affiliations

  • Mila Ljujic
    • 1
  • Sanja Mijatovic
    • 2
  • Mirna Z. Bulatovic
    • 2
  • Marija Mojic
    • 2
  • Danijela Maksimovic-Ivanic
    • 2
  • Dragica Radojkovic
    • 1
  • Aleksandra Topic
    • 3
    Email author
  1. 1.Institute of Molecular Genetics and Genetic EngineeringUniversity of BelgradeBelgradeSerbia
  2. 2.Institute for Biological Research “Sinisa Stankovic”University of BelgradeBelgradeSerbia
  3. 3.Department of Medical Biochemistry, Faculty of PharmacyUniversity of BelgradeBelgradeSerbia

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