KIST‐A164A Increases a Quinone Reductase Potentially by Inhibiting COX‐2‐Dependent Inflammatory Signaling

Abstract

The up‐regulation of phase II detoxification genes is believed to play an important role in cancer prevention. Cyclooxygenase‐2 (COX‐2) is often up‐regulated in human colorectal cancers, and it is considered as one of major inflammatory factors causing carcinogenesis. However, the relationship between the induction of phase II enzyme and COX‐2 activation in terms of cancer prevention is unknown. We have identified a polyacetylene compound (KIST‐A164A) from Aster koraiensis as a major principle for a significant quinone reductase (QR) induction via transcriptional activation. We also found that KIST‐A164A significantly inhibited COX‐2 mRNA expression levels and PGE2 production in a dose‐dependent manner. Further molecular study revealed that co‐treatment with KIST‐A164A and acetylsalicylic acid, an inhibitor of COX‐2, increased the expression of QR mRNA and protein levels, which was coincidently enhancing QR activity as well as antioxidant response element (ARE) activation in Caco‐2 cells. The ARE activation was increased 2‐fold over control when the cells were treated with 50 μM KIST‐A164A in the presence of JNK1/2 inhibitor, SP600125. Taken together, we present here that KIST‐A164A increases QR through ARE and it could be related to inhibition of COX‐2‐dependent inflammatory signaling.