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Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

  • Review Article
  • Theme: Natural Products as Therapeutic Modulators
  • Published:
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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.

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Abbreviations

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

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Acknowledgement

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).

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  1. Graduate Program in Pharmaceutical Science, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA

    Ka Lung Cheung

  2. Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey, 08854, USA

    Ah-Ng Kong

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  1. Ka Lung Cheung
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Correspondence to Ah-Ng Kong.

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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

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