Psoralidin, a dual inhibitor of COX-2 and 5-LOX, regulates ionizing radiation (IR)-induced pulmonary inflammation

详细信息    查看全文

• 作者：Hee Jung Yang^a ; ¹ ; HyeSook Youn^b ; ¹ ; Ki Moon Seong^c ; ¹ ; Young Ju Yun^a ; Wanyeon Kim^a ; Young Ha Kim^a ; Ji Young Lee^a ; Cha Soon Kim^c ; Young-Woo Jin^c ; BuHyun Youn^a ; ^{bhyoun72@pusan.ac.kr"" rel=""nofollow}
• 关键词：Ionizing radiation ; Psoralidin ; COX-2 ; 5-LOX ; Anti-inflammation
• 刊名：Biochemical Pharmacology
• 出版年：2011
• 出版时间：1 September 2011
• 年：2011
• 卷：82
• 期：5
• 页码：524-534
• 全文大小：1343 K

文摘

Radiotherapy is the most significant non-surgical cure for the elimination of tumor, however it is restricted by two major problems: radioresistance and normal tissue damage. Efficiency improvement on radiotherapy is demanded to achieve cancer treatment. We focused on radiation-induced normal cell damage, and are concerned about inflammation reported to act as a main limiting factor in the radiotherapy. Psoralidin, a coumestan derivative isolated from the seed of Psoralea corylifolia, has been studied for anti-cancer and anti-bacterial properties. However, little is known regarding its effects on IR-induced pulmonary inflammation. The aim of this study is to investigate mechanisms of IR-induced inflammation and to examine therapeutic mechanisms of psoralidin in human normal lung fibroblasts and mice. Here, we demonstrated that IR-induced ROS activated cyclooxygenases-2 (COX-2) and 5-lipoxygenase (5-LOX) pathway in HFL-1 and MRC-5 cells. Psoralidin inhibited the IR-induced COX-2 expression and PGE₂ production through regulation of PI3K/Akt and NF-κB pathway. Also, psoralidin blocked IR-induced LTB₄ production, and it was due to direct interaction of psoralidin and 5-lipoxygenase activating protein (FLAP) in 5-LOX pathway. IR-induced fibroblast migration was notably attenuated in the presence of psoralidin. Moreover, in vivo results from mouse lung indicate that psoralidin suppresses IR-induced expression of pro-inflammatory cytokines (TNF-α, TGF-β, IL-6 and IL-1 α/β) and ICAM-1. Taken together, our findings reveal a regulatory mechanism of IR-induced pulmonary inflammation in human normal lung fibroblast and mice, and suggest that psoralidin may be useful as a potential lead compound for development of a better radiopreventive agent against radiation-induced normal tissue injury.