Areca nut extracts increased the expression of cyclooxygenase-2, prostaglandin E2 and interleukin-1α in human immune cells via oxidative stress

Background and objectives: Areca nut has been identified as a carcinogen. Inflammation reveals a strong link with tumourigenesis. The aim of this study was to investigate the effects of areca nut on the expression of the key pro-inflammatory mediators involved in malignancy, cyclooxygenase-2 (COX-2), prostaglandin E-2 (PGE(2)), interleukin (IL)-1 alpha and nuclear factor-kappa B (NF-kappa B), by human immune cells. The role of oxidative stress was also examined. Materials and methods: Human peripheral blood mononuclear cells (PBMCs) were treated with extracts of ripe areca nut (rANE) or tender areca nut (tANE). Expression of pro-inflammatory mediators was assayed using Western blotting, reverse transcription-polymerase chain reaction, competitive enzyme immunoassay or enzyme-linked immunosorbent assay (ELISA). Activity of NF-kappa B was evaluated using an ELISA-based method. Results: Both rANE and tANE enhanced the expression of COX-2, PGE(2) and IL-1 alpha by PBMCs. The secretion of PGE(2) was induced by rANE (<= 20-40 mu g ml(-1)) and tANE (<= 160 mu g ml(-1)) significantly in a dose- and time-dependent manner. However, the above enhancing effects of ANEs could be attenuated by antioxidants. ANEs also increased the nuclear,expression of the redox-sensitive factor NF-kappa B. Conclusions: The results demonstrate that ANEs induced the expression of pro-inflammatory mediators mainly through the induction of oxidative stress and implicate the possibility of using antioxidants for disease prevention. (C) 2013 Elsevier Ltd. All rights reserved.