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Resveratrol causes COX-2- and p53-dependent apoptosis in head and neck squamous cell cancer cells

Hung-Yun Lin1, Mingzeng Sun, Heng-Yuan Tang

  • 1Signal Transduction Laboratory, Ordway Research Institute, 150 New Scotland Avenue, Albany, New York 12208, USA. hlin@ordwayresearch.org

Journal of Cellular Biochemistry
|May 1, 2008
PubMed

Insights

Resveratrol induces apoptosis in head and neck cancer cells by activating ERK1/2, leading to nuclear COX-2 accumulation, which is essential for p53 activation and cancer cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cyclooxygenase-2 (COX-2) is upregulated in various tumor cells.
  • Resveratrol, a stilbene, exhibits pro-apoptotic effects in numerous cancer cell lines.
  • Understanding resveratrol's apoptotic mechanism in head and neck cancer is crucial.

Purpose of the Study:

  • To elucidate the mechanism of resveratrol-induced apoptosis in human head and neck squamous cell carcinoma UMSCC-22B cells.
  • To investigate the role of cellular Cyclooxygenase-2 (COX-2) in this process.
  • To determine the involvement of ERK1/2 and p53 signaling pathways.

Main Methods:

  • UMSCC-22B cells were treated with resveratrol and analyzed for apoptosis.
  • Western blotting and chromatin immunoprecipitation were used to assess protein levels and promoter binding.
  • Inhibitors of ERK1/2 and p53, as well as COX-2 siRNA, were employed to dissect the signaling cascade.

Main Results:

  • Resveratrol-induced apoptosis was concentration-dependent and linked to ERK1/2 activation and p53 phosphorylation/nuclear accumulation.
  • Resveratrol increased nuclear COX-2 accumulation, dependent on ERK1/2 but not p53.
  • COX-2 inhibition or knockdown blocked p53 activation and resveratrol-induced apoptosis.

Conclusions:

  • Resveratrol triggers apoptosis in UMSCC-22B cells via a pathway involving ERK1/2 activation and subsequent nuclear COX-2 accumulation.
  • Nuclear COX-2 is essential for p53 activation and p53-dependent apoptosis in these cancer cells.
  • The ERK1/2-COX-2-p53 axis represents a key mechanism for resveratrol's anti-cancer effects in head and neck squamous cell carcinoma.

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