6-azauridine induces autophagy-mediated cell death via a p53-and AMPK-dependent pathwayopen access
- Authors
- Cha, Yeo-Eun; Park, Rackhyun; Jang, Minsu; Park, Yea-In; Yamamoto, Ayane; Oh, Won Keun; Lee, Eun-Ju; Park, Junsoo
- Issue Date
- Mar-2021
- Publisher
- MDPI AG
- Keywords
- 6-azauridine; Autophagic flux; Autophagy; Autophagy-mediated cell death
- Citation
- International Journal of Molecular Sciences, v.22, no.6
- Journal Title
- International Journal of Molecular Sciences
- Volume
- 22
- Number
- 6
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/48371
- DOI
- 10.3390/ijms22062947
- ISSN
- 1661-6596
1422-0067
- Abstract
- 6-Azauridine (6-AZA), a pyrimidine nucleoside analogue, is known to exhibit both anti-tumor and antiviral activities. Although 6-AZA was discovered more than 60 years ago, the cellular effects of this compound are yet to be elucidated. Here, we report that 6-AZA regulates autophagy-mediated cell death in various human cancer cells, where 6-AZA treatment activates autophagic flux through the activation of lysosomal function. Furthermore, 6-AZA exhibited cytotoxicity in all cancer cells studied, although the mechanisms of action were diverse. In H460 cells, 6-AZA treatment induced apoptosis, and the extent of the latter could be reduced by treatment with chloroquine (CQ), a lysosomal inhibitor. However, 6-AZA treatment resulted in cell cycle arrest in H1299 cells, which could not be reversed by CQ. The cytotoxicity associated with 6-AZA treatment could be linearly correlated to the degree of autophagy-mediated cell death. In addition, we demonstrated that the cytotoxic effect of 6-AZA was dependent on AMPK and p53. These results collectively in-dicate that autophagy-mediated cell death triggered by 6-AZA contributes to its antitumor effect. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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