Newly constructed stable reporter cell lines for mechanistic studies on electrophile-responsive element-mediated gene expression reveal a role for flavonoid planarity

Generation of a Stable Antioxidant Response Element–Driven Reporter Gene Cell Line and Its Use to Show Redox-Dependent Activation of Nrf2 by Cancer Chemotherapeutic Agents

“…Based on induction of reporter genes by t-BHQ, it is apparent that our AREc32 cells gave very substantially greater levels of induction than was found in HepG2 cells. A murine Hepa1c1c7 cell line stably transfected with the mouse 41-bp mouse gsta1-ARE driving the luciferase gene in pGL3-basic has been described recently (35), and it seems to give comparable levels of induction as we find in our AREc32 cells.…”

“…In this case, t-BHQ probably induces ARE-driven genes because it undergoes a two-electron oxidation to form an electrophilic quinone. Correlation of the relative abilities of t-BHQ and its analogue 2,5-di-tert-butylhydroquinone to induce rat GSTP1 with their relative redox-cycling activities, their abilities to produce superoxide, or their electrophilic properties has established that it is the last characteristic that is most important for activation of ARE-driven gene expression (35). In particular, Nakamura et al (36) found that t-BHQ can form a quinone and is a good inducer of GSTP1, whereas 2,5-di-tert-butylhydroquinone cannot form a quinone and is not a good inducer of GSTP1.…”

Induction of electrophile-responsive element (EpRE)-mediated gene expression by tomato extracts in vitro

“…In recent years, reporter gene assays have been developed with the goal to link bioactive compounds found in food products to beneficial health effects (Shih, Pickwell, & Quattrochi, 2000;Boerboom et al, 2006;Gijsbers et al, 2011). So far these assays have been mainly used to screen isolated pure compounds, but the assays have not yet been used to test extracts from fruits and vegetables to get an integral view of their potential effects on gene regulatory pathways.…”

Functionalized aurones as inducers of NAD(P)H:quinone oxidoreductase 1 that activate AhR/XRE and Nrf2/ARE signaling pathways: Synthesis, evaluation and SAR

“…This feature may not be adequately captured by the existing descriptors used in the QSAR analysis and E LUMO may indirectly reflect the conformational change. The importance of conformational planarity was highlighted by the failure of the non-planar flavonoid taxifolin to activate ARE-mediated gene expression compared with other planar flavonoids like quercetin and fisetin [50]. The explanation was that interaction with Keap1 or other effector/receptor protein involves a stereospecific interaction which was diminished in a non-planar compound.…”