Radiation-induced cyclooxygenase 2 up-regulation is dependent on redox status in prostate cancer cells

• Published in: Radiation research Vol. 160; no. 6; p. 617
• Main Authors: Li, Lingyun, Steinauer, Kirsten K, Dirks, Amie J, Husbeck, Bryan, Gibbs, Iris, Knox, Susan J
• Format: Journal Article
• Language: English
• Published: United States 01.12.2003
• Subjects: Cell Line, Tumor; Cyclooxygenase 2; Dinoprostone - analysis; Glutathione - analysis; Humans; Isoenzymes - analysis; Male; Membrane Proteins; Oxidation-Reduction; Prostaglandin-Endoperoxide Synthases - analysis; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; Reactive Oxygen Species; Up-Regulation
• ISSN: 0033-7587
• DOI: 10.1667/RR3076

Cyclooxygenase 2 (COX2) is the inducible isozyme of COX, a key enzyme in arachidonate metabolism and the conversion of arachidonic acid (AA) to prostaglandins (PGs) and other eicosanoids. Previous studies have demonstrated that the COX2 protein is up-regulated in prostate cancer cells after irradiation and that this results in elevated levels of PGE(2). In the present study, we further investigated whether radiation-induced COX2 up-regulation is dependent on the redox status of cells from the prostate cancer cell line PC-3. l-Buthionine sulfoximine (BSO), which inhibits gamma glutamyl cysteine synthetase (gammaGCS), and the antioxidants alpha-lipoic acid and N-acetyl-l-cysteine (NAC) were used to modulate the cellular redox status. BSO decreased the cellular GSH level and increased cellular reactive oxygen species (ROS) in PC-3 cells, whereas alpha-lipoic acid and NAC increased the GSH level and decreased cellular ROS. Both radiation and the oxidant H(2)O(2) had similar effects on COX2 up-regulation and PGE(2) production in PC-3 cells, suggesting that radiation-induced COX2 up-regulation is secondary to the production of ROS. The relative increases in COX2 expression and PGE(2) production induced by radiation and H(2)O(2) were even greater when PC-3 cells were pretreated with BSO. When the cells were pretreated with alpha-lipoic acid or NAC for 24 h, both radiation- and H(2)O(2)-induced COX2 up-regulation and PGE(2) production were markedly inhibited. These results demonstrate that radiation-induced COX2 up-regulation in prostate cancer cells is modulated by the cellular redox status. Radiation-induced increases in ROS levels contribute to the adaptive response of PC-3 cells, resulting in elevated levels of COX2.