Imidazole inhibits autophagy flux by blocking autophagic degradation and triggers apoptosis via increasing FoxO3a-Bim expression

  • Authors:
    • Zhenxing Liu
    • Yingzheng Wang
    • Shuan Zhao
    • Jingyou Zhang
    • Yi Wu
    • Shenming Zeng
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  • Published online on: November 21, 2014     https://doi.org/10.3892/ijo.2014.2771
  • Pages: 721-731
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Abstract

Imidazole, an organic alkaloid, is an important pharmacophore in drug discovery. Anti-neoplastic potential of imidazole derivatives has been documented in several studies; however, mechanisms by which tumor cells respond to these stimuli remain to be elucidated. Autophagy and apoptosis have key roles in tumorigenesis and tumor treatment. In this study, we systematically examined autophagic events induced by imidazole in HEC‑1B cells. Accumulation of autophagic vacuoles in imidazole-treated cells was verified by conversion of LC3 protein, as well as confocal and transmission electron microscopy. Furthermore, imidazole blocked autophagic degradation by impairing maturation of autophagosomes into autolysosomes. Concurrently, imidazole treatment induced apoptosis in HEC‑1B cells, accompanied by activation of caspase 9 and 3. The proapoptotic effect was mediated by increased Bim expression. Moreover, imidazole upregulated the protein level of Foxo3a and induced its increased nuclear localisation. In addition, siRNA-mediated silencing of FoxO3a effectively attenuated imidazole-induced Bim upregulation and cell death, indicating direct involvement of this pathway in the imidazole-induced apoptosis. Taken together, our data provided a molecular link between imidazoles and anticancer therapies; understanding of these properties of imidazole is essential for development of effective cancer therapeutics using imidazoles.
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February-2015
Volume 46 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Liu Z, Wang Y, Zhao S, Zhang J, Wu Y and Zeng S: Imidazole inhibits autophagy flux by blocking autophagic degradation and triggers apoptosis via increasing FoxO3a-Bim expression. Int J Oncol 46: 721-731, 2015.
APA
Liu, Z., Wang, Y., Zhao, S., Zhang, J., Wu, Y., & Zeng, S. (2015). Imidazole inhibits autophagy flux by blocking autophagic degradation and triggers apoptosis via increasing FoxO3a-Bim expression. International Journal of Oncology, 46, 721-731. https://doi.org/10.3892/ijo.2014.2771
MLA
Liu, Z., Wang, Y., Zhao, S., Zhang, J., Wu, Y., Zeng, S."Imidazole inhibits autophagy flux by blocking autophagic degradation and triggers apoptosis via increasing FoxO3a-Bim expression". International Journal of Oncology 46.2 (2015): 721-731.
Chicago
Liu, Z., Wang, Y., Zhao, S., Zhang, J., Wu, Y., Zeng, S."Imidazole inhibits autophagy flux by blocking autophagic degradation and triggers apoptosis via increasing FoxO3a-Bim expression". International Journal of Oncology 46, no. 2 (2015): 721-731. https://doi.org/10.3892/ijo.2014.2771