Amyloid β oligomers inhibit growth of human cancer cells

Autoři: Bozena Pavliukeviciene aff001;  Aiste Zentelyte aff002;  Marija Jankunec aff001;  Giedre Valiuliene aff002;  Martynas Talaikis aff001;  Ruta Navakauskiene aff002;  Gediminas Niaura aff001;  Gintaras Valincius aff001
Působiště autorů: Department of Bioelectrochemistry and Biospectroscopy, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania aff001;  Department of Molecular Cell Biology, Institute of Biochemistry, Life Sciences Center, Vilnius University, Vilnius, Lithuania aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0221563


Effects of amyloid beta (Aβ) oligomers on viability and function of cell lines such as NB4 (human acute promyelocytic leukemia), A549 (human lung cancer (adenocarcinomic alveolar basal epithelial tumor)) and MCF-7 (human breast cancer (invasive breast ductal carcinoma)) were investigated. Two types of Aβ oligomers were used in the study. The first type was produced in the presence of oligomerization inhibitor, hexafluoroisopropanol (HFIP). The second type of amyloids was assembled in the absence of the inhibitor. The first type preparation was predominantly populated with dimers and trimers, while the second type contained mostly pentadecamers. These amyloid species exhibited different secondary protein structure with considerable amount of antiparallel β sheet structural elements in HFIP oligomerized Aβ mixtures. The effect of the cell growth inhibition, which was stronger in the case of HFIP Aβ oligomers, was observed for all cell lines. Tests aiming at elucidating the effects of the amyloid species on cell cycles showed little differences between amyloid preparations. This prompts us to conclude that the effect on the cancer cell proliferation rate is less specific to the biological processes developing inside the cells during the proliferation. Therefore, cell growth inhibition may involve interactions with the peripheral parts of the cancer cells, such as a phospholipid membrane, and only in case of the NB4 cells, where accumulation of amyloid species inside the cells was detected, one may imply the opposite. In general, cancer cells were much less susceptible to the damaging effects of amyloid oligomers compared to earlier observations in mixed neuronal cell cultures.

Klíčová slova:

Biology and life sciences – Biochemistry – Proteins – Amyloid proteins – Cell biology – Cell processes – Cell cycle and cell division – Cell death – Apoptosis – Cell growth – Physical sciences – Materials science – Materials – Oligomers – Research and analysis methods – Chromatographic techniques – Liquid chromatography – High performance liquid chromatography – Medicine and health sciences – Oncology – Cancer treatment – Mental health and psychiatry – Dementia – Alzheimer's disease – Neurology – Neurodegenerative diseases


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