Alpha-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)
2016
Authors:
Ljujic, MilaMijatović, Sanja
Bulatović, Mirna
Mojić, Marija
Maksimović-Ivanić, Danijela
Radojkovic, Dragica
Topic, Aleksandra
Document Type:
Article (Published version)
,
© 2016 by the Izdatelstvo Nauka
Metadata
Show full item recordAbstract:
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.
Keywords:
Alpha-1 antitrypsin; Apoptosis; Autophagy; Colon cancer cell line (HCT116)Source:
Molekuliarnaia biologiia, 2016, 50, 1, 174-178Funding / projects:
- Molecular mechanisms of physiological and pharmacological control of inflammation and cancer (RS-MESTD-Basic Research (BR or ON)-173013)
- Complex diseases as a model system for phenotype modulation- structural and functional analysis of molecular biomarkers (RS-MESTD-Basic Research (BR or ON)-173008)
DOI: 10.7868/S0026898416010122
ISSN: 0026-8984