Role of ASC in hypoxia-mediated cell death in pancreatic cancer

  • Authors:
    • Takao Ohtsuka
    • Mayumi Mitsuno
    • Yoshihiko Kitajima
    • Takao Ide
    • Sam W. Lee
    • Kohji Miyazaki
  • View Affiliations

  • Published online on: November 1, 2008     https://doi.org/10.3892/mmr_00000035
  • Pages: 827-831
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Abstract

ASC, an apoptosis-associated speck-like protein, can regulate apoptosis in response to various types of cell death stimuli. In this study, we investigated the role of ASC in hypoxia-mediated cell death in pancreatic cancer. ASC was inducible under a 1% O2 hypoxic condition in pancreatic cancer cells, which was HIF1α-dependent but p53-independent. Two representative chemotherapeutic agents for pancreatic cancer, 5-fluorouracil and gemcitabine, promoted cell death in a p53-dependent manner; however, 1% hypoxia caused chemoresistance to these drugs. Western blot analysis of this condition showed that expression of Bax, a pro-apoptotic gene, decreased, while the anti-apoptotic genes IAP-2 and survivin increased. These results suggest that, although hypoxia induces both pro-apoptotic and anti-apoptotic genes, the total balance seems to be anti-apoptotic dominant, which might explain chemoresistance in pancreatic cancer. To overcome this anti-apoptotic dominant condition, we infected adenovirus-expressing ASC into pancreatic cancer cells. The expressed ASC induced cell death even under 20% normoxia, and was enhanced by hypoxia. Our data demonstrate the possible mechanism of chemoresistance under hypoxia in pancreatic cancer cells, thereby suggesting the potential use of ASC as a new treatment strategy for pancreatic cancer.

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November 2008
Volume 1 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Ohtsuka, T., Mitsuno, M., Kitajima, Y., Ide, T., Lee, S.W., & Miyazaki, K. (2008). Role of ASC in hypoxia-mediated cell death in pancreatic cancer. Molecular Medicine Reports, 1, 827-831. https://doi.org/10.3892/mmr_00000035
MLA
Ohtsuka, T., Mitsuno, M., Kitajima, Y., Ide, T., Lee, S. W., Miyazaki, K."Role of ASC in hypoxia-mediated cell death in pancreatic cancer". Molecular Medicine Reports 1.6 (2008): 827-831.
Chicago
Ohtsuka, T., Mitsuno, M., Kitajima, Y., Ide, T., Lee, S. W., Miyazaki, K."Role of ASC in hypoxia-mediated cell death in pancreatic cancer". Molecular Medicine Reports 1, no. 6 (2008): 827-831. https://doi.org/10.3892/mmr_00000035