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

Takao Ohtsuka, Mayumi Mitsuno, Yoshihiko Kitajima, Takao Ide, Sam W. Lee, Kohji Miyazaki

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 antiapoptotic dominant condition, we infected adenovirusexpressing 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.

Original languageEnglish
Pages (from-to)827-831
Number of pages5
JournalMolecular medicine reports
Volume1
Issue number6
DOIs
Publication statusPublished - Dec 1 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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  • Cite this

    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(6), 827-831. https://doi.org/10.3892/mmr-00000035