| Autor: |
Cha YE; Division of Biological Science and Technology, Yonsei University, Wonju 26493, Korea., Park R; Division of Biological Science and Technology, Yonsei University, Wonju 26493, Korea., Jang M; Division of Biological Science and Technology, Yonsei University, Wonju 26493, Korea., Park YI; Division of Biological Science and Technology, Yonsei University, Wonju 26493, Korea., Yamamoto A; Division of Biological Science and Technology, Yonsei University, Wonju 26493, Korea., Oh WK; Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea., Lee EJ; Department of Obstetrics and Gynecology, Chung-Ang University School of Medicine, Seoul 06974, Korea., Park J; Division of Biological Science and Technology, Yonsei University, Wonju 26493, Korea. |
| Abstrakt: |
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. |
