6-azauridine induces autophagy-mediated cell death via a p53-and AMPK-dependent pathway

Yeo Eun Cha, Rackhyun Park, Minsu Jang, Yea In Park, Ayane Yamamoto, Won Keun Oh, Eun Ju Lee, Junsoo Park

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


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.

Original languageEnglish
Article number2947
Pages (from-to)1-11
Number of pages11
JournalInternational journal of molecular sciences
Issue number6
Publication statusPublished - 2021 Mar 2

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


Dive into the research topics of '6-azauridine induces autophagy-mediated cell death via a p53-and AMPK-dependent pathway'. Together they form a unique fingerprint.

Cite this