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.
TY - JOUR
AU - Ljujić, Mila
AU - Mijatović, Sanja
AU - Bulatović, Mirna Z.
AU - Mojic, Marija
AU - Maksimović-Ivanić, Danijela
AU - Radojković, Dragica
AU - Topić, Aleksandra
PY - 2016
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2773
AB - 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.
PB - Maik Nauka/Interperiodica/Springer, New York
T2 - Molecular Biology
T1 - ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)
VL - 50
IS - 1
SP - 153
EP - 156
DO - 10.1134/S002689331601012X
ER -
@article{
author = "Ljujić, Mila and Mijatović, Sanja and Bulatović, Mirna Z. and Mojic, Marija and Maksimović-Ivanić, Danijela and Radojković, Dragica and Topić, Aleksandra",
year = "2016",
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.",
publisher = "Maik Nauka/Interperiodica/Springer, New York",
journal = "Molecular Biology",
title = "ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)",
volume = "50",
number = "1",
pages = "153-156",
doi = "10.1134/S002689331601012X"
}
Ljujić, M., Mijatović, S., Bulatović, M. Z., Mojic, M., Maksimović-Ivanić, D., Radojković, D.,& Topić, A.. (2016). ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116). in Molecular Biology
Maik Nauka/Interperiodica/Springer, New York., 50(1), 153-156.
https://doi.org/10.1134/S002689331601012X
Ljujić M, Mijatović S, Bulatović MZ, Mojic M, Maksimović-Ivanić D, Radojković D, Topić A. ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116). in Molecular Biology. 2016;50(1):153-156.
doi:10.1134/S002689331601012X .
Ljujić, Mila, Mijatović, Sanja, Bulatović, Mirna Z., Mojic, Marija, Maksimović-Ivanić, Danijela, Radojković, Dragica, Topić, Aleksandra, "ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)" in Molecular Biology, 50, no. 1 (2016):153-156,
https://doi.org/10.1134/S002689331601012X . .
