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

Abstract

Cyclooxygenase-2 (COX-2) content is increased in many types of tumor cells. We have investigated the mechanism by which resveratrol, a stilbene that is pro-apoptotic in many tumor cell lines, causes apoptosis in human head and neck squamous cell carcinoma UMSCC-22B cells by a mechanism involving cellular COX-2. UMSCC-22B cells treated with resveratrol for 24 h, with or without selected inhibitors, were examined: (1) for the presence of nuclear activated ERK1/2, p53 and COX-2, (2) for evidence of apoptosis, and (3) by chromatin immunoprecipitation to demonstrate p53 binding to the p21 promoter. Stilbene-induced apoptosis was concentration-dependent, and associated with ERK1/2 activation, serine-15 p53 phosphorylation and nuclear accumulation of these proteins. These effects were blocked by inhibition of either ERK1/2 or p53 activation. Resveratrol also caused p53 binding to the p21 promoter and increased abundance of COX-2 protein in UMSCC-22B cell nuclei. Resveratrol-induced nuclear COX-2 accumulation was dependent upon ERK1/2 activation, but not p53 activation. Activation of p53 and p53-dependent apoptosis were blocked by the COX-2 inhibitor, NS398, and by transfection of cells with COX-2-siRNA. In UMSCC-22B cells, resveratrol-induced apoptosis and induction of nuclear COX-2 accumulation share dependence on the ERK1/2 signal transduction pathway. Resveratrol-inducible nuclear accumulation of COX-2 is essential for p53 activation and p53-dependent apoptosis in these cancer cells.

Aspirin blocks growth of breast tumor cells and tumor-initiating cells and induces reprogramming factors of mesenchymal to epithelial transition

“…Mechanistically, it has been proposed that the anticancer effect of ASA is mediated through COX-dependent 36,37,57,58 and -independent pathways. 53,54,59 Recent studies have shown that MCF-7 mammospheres are insensitive to the cyclooxygenase pathway, and the COX-2 inhibitor (Indomethacin) was unable to reduce the mammosphere-forming capacity of MDA-MB-231 cells.…”

Resveratrol Protects Human Endothelium from H2O2-Induced Oxidative Stress and Senescence via SirT1 Activation

“…It possesses the ability to scavenge oxidatively generated free radicals, and prevents tumor progression by blocking NF-B expression, leading to cancer cell apoptosis 16,[23][24][25][26][27] . RV also has promising neuroprotective and cardioprotective effects, as well as slowing aging and delaying the onset of chronic diseases 23,[28][29][30] .…”

Gallotannin regulates apoptosis and COX-2 expression via Akt and p38kinase pathway in human lung cancer cell line, A549

“…Also, several studies have reported that resveratrol, a pharmacological inducer of COX-2, is capable of inducing p53-dependent apoptosis by implicating of COX-2 expression in a variety of cell types such as breast, thyroid, head and neck squamous cancer cells. Therefore, COX-2 has both positive and negative functions on a case-by-case basis in cancer cells (Lin et al 2008). Thus, COX-2 and p53 have an unsteady relationship that can be related to cell growth and apoptosis.…”