Molecular basis of chemoprevention with dietary phytochemicals: redox-regulated transcription factors as relevant targets

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Abstract

A precise regulation of redox balance is required for the cellular homeostatic control. Aberrant activation of redox-sensitive transcription factors, such as nuclear factor-kappaB (NF-κB), activator protein 1 (AP-1), cyclic adenosine monophosphate response element binding protein (CREB), and hypoxia inducible factor (HIF), contributes to carcinogenesis by promoting persistent inflammation, abnormal cell proliferation, evasion from apoptosis, angiogenesis, etc. A wide variety of dietary phytochemicals have been reported to exert cancer chemopreventive properties by suppressing the inappropriate activation of aforementioned transcription factors. On the other hand, transcription of genes involved in the activation of cellular antioxidant arsenal and carcinogen detoxification is largely regulated by another redox-sensitive transcription factor, i.e. NF-E2 related factor 2 (Nrf2), which plays a role in protecting cells/tissues from oxidative or electrophilic damage. Some food-derived phytochemicals have been shown to activate Nrf2, thereby augmenting cellular antioxidant capacity and inducing expression of phase-2 detoxification enzymes. Therefore, the modulation of cellular signaling mediated by redox-sensitive transcription factors in the right direction represents a promising approach to achieving molecular target-based chemoprevention with edible phytochemicals.

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