title: [Alpha-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)].
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-κB. 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.
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Ljujic
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Belgrade, Serbia.
authors.forename: S
authors.initials: S
authors.lastname: Mijatovic
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Belgrade, Serbia.
authors.forename: M Z
authors.initials: MZ
authors.lastname: Bulatovic
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Mojic
authors.affiliation: Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Maksimovic-Ivanic
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Radojkovic
authors.affiliation: Institute of Medical Biochemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.|aleksandra.topic1@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Topic
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045325:HCT116 Cells; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000494:pharmacology*
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D009570:Nitriles; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000515:alpha 1-Antitrypsin; C113580:U 0126
keywords: alpha-1 antitrypsin; apoptosis; autophagy; colon cancer cell line (HCT116)