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Scientific paper - Original scientific paper
5-Aminoimidazole-4-carboxamide ribonucleoside-induced autophagy flux during differentiation of monocytic leukemia cells
Cell Death Discovery, 3 (2017); 17066. https://doi.org/10.1038/cddiscovery.2017.66
Dembitz, Vilma; Lalić, Hrvoje; Višnjić, Dora

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Dembitz, V., Lalić, H. & Višnjić, D. (2017). 5-Aminoimidazole-4-carboxamide ribonucleoside-induced autophagy flux during differentiation of monocytic leukemia cells. Cell Death Discovery, 3., 17066. doi: 10.1038/cddiscovery.2017.66

Dembitz, Vilma, et al. "5-Aminoimidazole-4-carboxamide ribonucleoside-induced autophagy flux during differentiation of monocytic leukemia cells." Cell Death Discovery, vol. 3, 2017, p. 17066. https://doi.org/10.1038/cddiscovery.2017.66

Dembitz, Vilma, Hrvoje Lalić and Dora Višnjić. "5-Aminoimidazole-4-carboxamide ribonucleoside-induced autophagy flux during differentiation of monocytic leukemia cells." Cell Death Discovery 3 (2017): 17066. https://doi.org/10.1038/cddiscovery.2017.66

Dembitz, V., Lalić, H. and Višnjić, D. (2017) '5-Aminoimidazole-4-carboxamide ribonucleoside-induced autophagy flux during differentiation of monocytic leukemia cells', Cell Death Discovery, 3, p. 17066. doi: 10.1038/cddiscovery.2017.66

Dembitz V, Lalić H, Višnjić D. 5-Aminoimidazole-4-carboxamide ribonucleoside-induced autophagy flux during differentiation of monocytic leukemia cells. Cell Death Discovery [Internet]. 2017 October 02 [cited 2024 December 30];3:17066. doi: 10.1038/cddiscovery.2017.66

V. Dembitz, H. Lalić and D. Višnjić, "5-Aminoimidazole-4-carboxamide ribonucleoside-induced autophagy flux during differentiation of monocytic leukemia cells", Cell Death Discovery, vol. 3, p. 17066, October 2017. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:105:431849. [Accessed: 30 December 2024]

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Metadata
Title (english)5-Aminoimidazole-4-carboxamide ribonucleoside-induced autophagy flux during differentiation of monocytic leukemia cells
AuthorVilma Dembitz
AuthorHrvoje Lalić
AuthorDora Višnjić
Author's institutionUniversity of Zagreb
School of Medicine
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Abstract (english)
Pharmacological modulators of AMP-dependent kinase (AMPK) have been suggested in treatment of cancer. The biguanide metformin and 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) have been reported to inhibit proliferation of solid tumors and hematological malignancies, but their role in differentiation is less explored. Our previous study demonstrated that AICAR alone induced AMPK-independent expression of differentiation markers in monocytic U937 leukemia cells, and no such effects were observed in response to metformin. The aim of this study was to determine the mechanism of AICAR-mediated effects and to test for the possible role of autophagy in differentiation of leukemia cells. The results showed that AICAR-mediated effects on the expression of differentiation markers were not mimicked by A769662, a more specific direct AMPK activator. Long-term incubation of U937 cells with AICAR and other differentiation agents, all-trans-retinoic acid (ATRA) and phorbol 12-myristate 13-acetate, increased the expression of the autophagy marker LC3B-II, and these effects were not observed in response to metformin. Western blot and immunofluorescence analyses of U937 cells treated with bafilomycin A1 or transfected with mRFP-GFP-LC3 proved that the increase in the expression of LC3B-II was due to an increase in autophagy flux, and not to a decrease in lysosomal degradation. 3-Methyladenine inhibited the expression of differentiation markers in response to all inducers, but had stimulatory effects on autophagy flux at dose that effectively inhibited the production of phosphatidylinositol 3-phosphate. The small inhibitory RNA-mediated down-modulation of Beclin 1 and hVPS34 had no effects on AICAR and ATRA-mediated increase in the expression of differentiation markers. These results show that AICAR and other differentiation agents induce autophagy flux in U937 cells and that the effects of AICAR and ATRA on the expression of differentiation markers do not depend on the normal levels of key proteins of the classical or canonical autophagy pathway.
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review
Publication versionPublished version
Journal titleCell Death Discovery
Numberingvol. 3, p. 17066
p-ISSN2058-7716
DOIhttps://doi.org/10.1038/cddiscovery.2017.66
URN:NBNurn:nbn:hr:105:431849
Publication2017-10-02
Document URLhttps://doi.org/10.1038/cddiscovery.2017.66
Type of resourceText
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2024-03-28 09:04:53