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

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Nutraceuticals and Cancer

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.

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Abbreviations

4E-BP1:

eIF4E binding protein

AR:

androgen receptor

AUC:

area under the curve

BP:

benzo[a]pyrene

Cdk:

cyclin-dependent kinase

C max :

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

T max :

time to reach C max

TRAMP:

transgenic adenocarcinoma of mouse prostate

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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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Authors and Affiliations

  1. Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    Anna A. Powolny & Shivendra V. Singh

  2. Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy & Nursing, Wilkes University, Wilkes-Barre, PA, USA

    Ajay Bommareddy

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  1. Anna A. Powolny
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  2. Ajay Bommareddy
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  3. Shivendra V. Singh
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Correspondence to Shivendra V. Singh .

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  1. , Barbara Ann Karmanos Cancer Institute, Department of Pathology, John R Street, Detroit, 48201, USA

    Fazlul H. Sarkar

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Powolny, A.A., Bommareddy, A., Singh, S.V. (2012). Slow but Steady Progress in Cancer Chemoprevention with Phenethyl Isothiocyanate: Fulfilled Promises and Translational Challenges. In: Sarkar, F. (eds) Nutraceuticals and Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2630-7_12

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