Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention.
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 NFkappaB, 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.
Cheung
Ka Lung
KL
Graduate Program in Pharmaceutical Science, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
Kong
Ah-Ng
AN
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D004032:Diet; D004790:Enzyme Induction; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017879:Isothiocyanates / Q000008:administration & dosage / Q000494:pharmacology*; D000072019:Kelch-Like ECH-Associated Protein 1; D020935:MAP Kinase Signaling System; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000517:prevention & control*; D013454:Sulfoxides; D013861:Thiocyanates / Q000008:administration & dosage / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D017879:Isothiocyanates; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D013454:Sulfoxides; D013861:Thiocyanates; C058305:phenethyl isothiocyanate; C016766:sulforaphane