The AAPS Journal

, Volume 12, Issue 1, pp 87–97

Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

Review Article Theme: Natural Products as Therapeutic Modulators

DOI: 10.1208/s12248-009-9162-8

Cite this article as:
Cheung, K.L. & Kong, AN. AAPS J (2010) 12: 87. doi:10.1208/s12248-009-9162-8

Abstract

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.

Key words

dietary cancer chemopreventionNF-kBNrf2phenethyl isothiocyanatesulforaphane

Abbreviations/acronyms

ARE/EpRE

Antioxidant/electrophile response element

COX-2

Cyclooxygenase-2

CYP

Cytochrome P450

DME

Drug-metabolizing enzyme

ERK

Extracellular signal-regulated kinase

GST

Glutathione-S-transferase

HO-1

Heme-oxygenase 1

IAP

Inhibitor of apoptosis

iNOS

Inducible nitric oxide synthase

ITCs

Isothiocyanates

IκB

Inhibitor of kappa B

IκK

IκB kinase

JNK

c-Jun N-terminal kinase

MAPK

Mitogen-activated protein kinase

NFκB

Nuclear factor kappa B

NQO

NAD(P)H:quinone oxidoreductase

Nrf2

NF-E2-related factor-2

PEITC

Penethyl isothiocyanate

RANKL

Receptor activator of NFκB ligand

ROS

Reactive oxygen species

RT-PCR

Reverse-transcription polymerase chain reaction

SFN

Sulforaphane

TNF

Tumor necrosis factor

UGT

UDP-glucuronosyltransferase

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  1. 1.Graduate Program in Pharmaceutical Science, Department of Pharmaceutics, Ernest Mario School of Pharmacy, RutgersThe State University of New JerseyPiscatawayUSA
  2. 2.Department of Pharmaceutics, Ernest Mario School of Pharmacy, RutgersThe State University of New JerseyPiscatawayUSA