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

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Pathology & Oncology Research

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.

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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.

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Authors and Affiliations

  1. Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, Belgrade, 11221, Serbia

    Mila Ljujic & Dragica Radojkovic

  2. Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Bulevar despota Stefana 142, Belgrade, 11060, Serbia

    Sanja Mijatovic, Mirna Z. Bulatovic, Marija Mojic & Danijela Maksimovic-Ivanic

  3. Department of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, 11221, Serbia

    Aleksandra Topic

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  1. Mila Ljujic
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  2. Sanja Mijatovic
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Ljujic, M., Mijatovic, S., Bulatovic, M.Z. et al. Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines. Pathol. Oncol. Res. 23, 335–343 (2017). https://doi.org/10.1007/s12253-016-0104-3

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