On the Cover:
Synthetic triterpenoids are potent inducers of phase 2 enzymes in vitro as well as inhibitors of inflammation in vivo. These properties make triterpenoids attractive candidates for cancer chemoprevention, prompting Yates et al., to evaluate one of the most potent triterpenoids, CDDO-Im, as a chemopreventive agent against aflatoxininduced tumorigenesis in rats. CDDO-Im engendered an 85% reduction in the hepatic focal burden of preneoplastic lesions (glutathione S-transferase P positive foci) when administered at 1 more potent than oltipraz, an established modulator of aflatoxin metabolism in humans, in this rat antitumorigenesis model (top panel). The graph is superimposed onto an image of two GST-P positive foci (photograph taken by Dr. Vince Memoli, Dartmouth-Hitchcock Medical Center, Lebanon, NH). The two GST-PNed cytoprotective genes in manner dependent upon the transcription factor Nrf2. The bottom panel shows the proposed pathway for induction of Nrf2-regulated cytoprotective genes by CDDO-Im. The unparalleled in vivo potency of CDDO-Im highlights the chemopreventive promise of targeting the Nrf2 signaling pathway with triterpenoids.