Autophagy and cell death signaling following dietary sulforaphane act independently of each other and require oxidative stress in pancreatic cancer

  • Authors:
    • Patrick Naumann
    • Franco Fortunato
    • Hanswalter Zentgraf
    • Markus W. Büchler
    • Ingrid Herr
    • Jens Werner
  • Corresponding author:
  • View Affiliations

  • Published online on: Friday, April 29, 2011
  • Pages: 101-109 DOI: 10.3892/ijo.2011.1025

Abstract

The broccoli isothiocyanate, sulforaphane (SFN), was recently identified as being capable of eliminating highly therapy-resistant pancreatic carcinoma (PC) cells without inducing toxic side effects. While SFN has been shown to stimulate autophagy or ‘self-eating’, it is unclear whether this catabolic process is a pro- or anti-tumorigenic response. To investigate the role of autophagy in SFN-induced cell death, established PC cell lines were treated with SFN, and the induction of autophagy was evaluated by detecting the abundance of autophagic vesicles by electron microscopy, the increase in converted LC3-II by Western blot analysis and the autophagosome puncta of GFP-LC3 by immunofluorescence. SFN-induced autophagy was suppressed by the autophagy inhibitor chloroquine, while the autophagy inducer rapamycin did not further enhance autophagy in PC cells. Importantly, neither modulator altered SFN cytotoxicity, suggesting that SFN-induced autophagy and cell death act independently of each other. In contrast, the antioxidant N-acetyl-cysteine sustained cell viability and prevented autophagy induction after SFN exposure, indicating that both signaling pathways depend on reactive oxygen species (ROS). Our studies provide a valuable new mechanistic insight into the SFN-induced elimination of PC cells and suggest that an SFN-enriched diet potentially enhances ROS-releasing chemotherapeutic agents.
Journal Cover

July 2011
Volume 39 Issue 1

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

2013 Impact Factor: 2.773
2014 I.F. (Expected) ≥ 3.310 Ranked #30/202 Oncology
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APA
Naumann, P., Fortunato, F., Zentgraf, H., Büchler, M.W., Herr, I., & Werner, J. (2011). Autophagy and cell death signaling following dietary sulforaphane act independently of each other and require oxidative stress in pancreatic cancer. International Journal of Oncology, 39, 101-109. http://dx.doi.org/10.3892/ijo.2011.1025
MLA
Naumann, P., Fortunato, F., Zentgraf, H., Büchler, M. W., Herr, I., Werner, J."Autophagy and cell death signaling following dietary sulforaphane act independently of each other and require oxidative stress in pancreatic cancer". International Journal of Oncology 39.1 (2011): 101-109.
Chicago
Naumann, P., Fortunato, F., Zentgraf, H., Büchler, M. W., Herr, I., Werner, J."Autophagy and cell death signaling following dietary sulforaphane act independently of each other and require oxidative stress in pancreatic cancer". International Journal of Oncology 39, no. 1 (2011): 101-109. http://dx.doi.org/10.3892/ijo.2011.1025