Regulation of Nrf2, NF-kappaB, and AP-1 signaling pathways by chemopreventive agents.

The inhibition of carcinogenesis by chemopreventive agents has been demonstrated in many tumorigenesis animal models. The chemopreventive mechanisms of those phytochemicals have been investigated extensively, though mostly in in vitro cell culture systems. The cellular signaling cascades mediated by transcription factors, including nuclear factor E2-related factor 2 (Nrf2), nuclear factor-kappaB (NF-kappaB), and activator protein-1 (AP-1), have been shown to play pivotal roles in tumor initiation, promotion, and progression processes. Thus, as demonstrated by previous substantive mechanistic studies, they appear to be ideal targets for cancer chemoprevention. In this review, we discuss the current progress and future challenges on our understanding of the molecular mechanisms in cancer chemoprevention by phytochemicals, focusing on the regulation of Nrf2, NF-kappaB, and AP-1 signaling pathways. Antioxid. Redox Signal. 7, 1648-1663.