Development of cancer is a long-term and multistep process which comprises initiation, progression, and promotion stages of carcinogenesis. Conceivably, it can be targeted and interrupted along these different stages. In this context, many naturally occurring dietary compounds from our daily consumption of fruits and vegetables have been shown to possess cancer preventive effects. Phenethyl isothiocyanate (PEITC) and sulforaphane (SFN) are two of the most widely investigated isothiocyanates from the crucifers. Both have been found to be very potent chemopreventive agents in numerous animal carcinogenesis models as well as cell culture models. They exert their chemopreventive effects through regulation of diverse molecular mechanisms. In this review, we will discuss the molecular targets of PEITC and SFN potentially involved in cancer chemoprevention. These include the regulation of drug-metabolizing enzymes phase I cytochrome P450s and phase II metabolizing enzymes. In addition, the signaling pathways including Nrf2–Keap 1, anti-inflammatory NFκB, apoptosis, and cell cycle arrest as well as some receptors will also be discussed. Furthermore, we will also discuss the similarities and their potential differences in the regulation of these molecular targets by PEITC and SFN.
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Antioxidant/electrophile response element
Extracellular signal-regulated kinase
Inhibitor of apoptosis
Inducible nitric oxide synthase
Inhibitor of kappa B
c-Jun N-terminal kinase
Mitogen-activated protein kinase
Nuclear factor kappa B
Receptor activator of NFκB ligand
Reactive oxygen species
Reverse-transcription polymerase chain reaction
Tumor necrosis factor
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We thank all the members in Dr. Tony Kong’s lab for their help in the discussion and preparation of this manuscript. We also thank Drs. Siwang Yu (Beijing University, People Republic of China) and Young-Sam Keum (Hormel Institute, Austin, MN) for their helpful discussions. This study was supported in part by Institutional Funds and by R01-CA073674, R01-CA094828 and R01-CA118947 to Dr Ah-Ng Tony Kong from the National Institutes of Health (NIH).
Guest Editor: Marilyn E. Morris
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Cheung, K.L., Kong, AN. Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention. AAPS J 12, 87–97 (2010). https://doi.org/10.1208/s12248-009-9162-8
- dietary cancer chemoprevention
- phenethyl isothiocyanate