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6-Azauridine Induces Autophagy-Mediated Cell Death via a p53- and AMPK-Dependent Pathway.

ABSTRACT: 6-Azauridine (6-AZA), a pyrimidine nucleoside analogue, is known to exhibit both antitumor 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 indicate that autophagy-mediated cell death triggered by 6-AZA contributes to its antitumor effect.

SUBMITTER: Cha YE

PROVIDER: S-EPMC8000275 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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6-Azauridine Induces Autophagy-Mediated Cell Death via a p53- and AMPK-Dependent Pathway.

Cha Yeo-Eun YE Park Rackhyun R Jang Minsu M Park Yea-In YI Yamamoto Ayane A Oh Won Keun WK Lee Eun-Ju EJ Park Junsoo J

International journal of molecular sciences 20210314 6

6-Azauridine (6-AZA), a pyrimidine nucleoside analogue, is known to exhibit both antitumor 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, al ...[more]

PMID: 33799444

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Dataset Information

6-Azauridine Induces Autophagy-Mediated Cell Death via a p53- and AMPK-Dependent Pathway.

Publications

6-Azauridine Induces Autophagy-Mediated Cell Death via a p53- and AMPK-Dependent Pathway.

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