Slow but Steady Progress in Cancer Chemoprevention with Phenethyl Isothiocyanate: Fulfilled Promises and Translational Challenges

  • Anna A. Powolny
  • Ajay Bommareddy
  • Shivendra V. Singh
Chapter

Abstract

Population-based observational studies continue to support the premise that intake of certain fruits and vegetables may lower the risk of cancer, and this association is quite persuasive for the cruciferous vegetables. Inverse association between cruciferous vegetable intake and the risk of cancer has been noted for different types of malignancies, including stomach, prostate, lung, breast, colon, and bladder cancers. Epidemiological observations in “FOLKS” have undoubtedly sparked interest among cancer biologists to conduct “FLASK”-based bench investigations to identify bioactive anticancer compounds from cruciferous vegetables as well as to determine their efficacy through “FUR”-based preclinical research in rodents. Cancer protective effect of cruciferous vegetables is partly attributed to organic isothiocyanates (ITC) with an –N = C = S functional group. Elucidation of the mechanism by which ITCs impart protection against cancer has been the topic of intense research in the past few decades. This article reviews bench-cage-bedside evidence supporting cancer chemopreventive potential of one such ITC compound, phenethyl isothiocyanate (PEITC). Future directions and challenges in clinical translation for PEITC are also highlighted.

Keywords

Prostate Cancer Cell LNCaP Cell Aberrant Crypt Focus Cruciferous Vegetable Macrophage Migration Inhibitory Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

4E-BP1

eIF4E binding protein

AR

androgen receptor

AUC

area under the curve

BP

benzo[a]pyrene

Cdk

cyclin-dependent kinase

Cmax

maximal achievable concentration

CYP

cytochrome P450

eIF4E

eukaryotic translation initiation factor 4E

ER

estrogen receptor

ERK

extracellular signal-regulated kinase

GST

glutathione S-transferase

ITCs

isothiocyanates

JNK

c-Jun N-terminal kinase

MAPK

mitogen-activated protein kinase

MMP

matrix metalloproteinase

NAC

N-acetylcysteine

NF-κB

nuclear factor-κB

NNK

4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

Nrf2

NF-E2 related factor-2

PEITC

phenethyl isothiocyanate

QR

NAD(P)H:quinone oxidoreductase

ROS

reactive oxygen species

Tmax

time to reach C max

TRAMP

transgenic adenocarcinoma of mouse prostate

Notes

Acknowledgements

Work cited from our laboratory was supported by the US PHS grant CA101753, awarded by the National Cancer Institute. Contributions of the present (Eun-Ryeong Hahm, Su-Hyeong Kim, Anuradha Sehrawat, Julie A Arlotti) and past members (Dong Xiao, Yan Zeng, Sunga Choi) of the Singh laboratory for preclinical studies on PEITC cited in this article are greatly appreciated.

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Anna A. Powolny
    • 1
  • Ajay Bommareddy
    • 2
  • Shivendra V. Singh
    • 1
  1. 1.Department of Pharmacology and Chemical BiologyUniversity of Pittsburgh School of Medicine, University of Pittsburgh Cancer InstitutePittsburghUSA
  2. 2.Department of Pharmaceutical SciencesNesbitt School of Pharmacy & Nursing, Wilkes UniversityWilkes-BarreUSA

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