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ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)

Authorized Users Only
2016
Authors
Ljujić, Mila
Mijatović, Sanja
Bulatović, Mirna Z.
Mojic, Marija
Maksimović-Ivanić, Danijela
Radojković, Dragica
Topić, Aleksandra
Article (Published version)
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Abstract
Alpha-1-antitrypsin (AAT), an acute phase protein, is the principal circulatory anti-protease. This multifunctional protein is encoded by the SERPINA1 gene. Although AAT was recognised as a potential tumour marker, its role in cancer biology remains unknown. Given that it has been demonstrated that AAT has an anti-apoptotic property against non-malignant cells, we aimed to investigate whether AAT affects apoptosis in a colon cancer cell line (HCT116). The presence of AAT in the HCT116 cell culture antagonized cytotoxicity of blockers of MEK1/2, PI3K/Akt pathways as well as NF-kappa B. The dominantly recovered cell viability was observed in the co-treatment with MEK1/2 inhibitor U0126. In addition, it was revealed that AAT almost completely abolished U0126-induced apoptosis through maintenance of the autophagy process. Our study revealed for the first time that the observed cyto-protection triggered by AAT was accompanied by sustained autophagy which opposed apoptosis. These results may... contribute to understanding of the role of AAT in cancer development and evaluation of efficacy of cancer therapy.

Source:
Molecular Biology, 2016, 50, 1, 153-156
Publisher:
  • Maik Nauka/Interperiodica/Springer, New York
Projects:
  • Molecular mechanisms of physiological and pharmacological control of inflammation and cancer (RS-173013)

DOI: 10.1134/S002689331601012X

ISSN: 0026-8933

WoS: 000378140200018

Scopus: 2-s2.0-84961873039
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URI
http://farfar.pharmacy.bg.ac.rs/handle/123456789/2773
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