Dietary Phenethyl Isothiocyanate Alters Gene Expression in Human Breast Cancer Cells

Young Jin Moon,Marilyn E Morris,Daniel A Brazeau

doi:10.1155/2011/462525

Abstract

Phenethyl isothiocyanate (PEITC), a component in cruciferous vegetables, can block chemical carcinogenesis in animal models. Our objective was to determine the effect of treatment with PEITC on gene expression changes in MCF-7 human breast cancer cells in order to evaluate potential mechanisms involved in its chemopreventive effects. MCF-7 cells were treated for 48 hours with either PEITC (3 μM) or the vehicle. Total RNA was extracted from cell membrane preparations, and labeled cDNA's representing the mRNA pool were reverse-transcribed directly from total RNA isolated for use in the microarray hybridizations. Two specific human GE Array Kits (Superarray Inc.) that both contain 23 marker genes, related to signal transduction pathways or cancer/tumor suppression, plus 2 housekeeping genes (β-actin and GAPDH), were utilized. Arrays from treated and control cells (n = 4 per group) were evaluated using a Student's t-test. Gene expression was significantly induced for tumor protein p53 (p53), cyclin-dependent kinase inhibitor 1C (p57 Kip2), breast cancer Type 2 early onset (BRCA2), cAMP responsive element binding protein 2 (ATF-2), interleukin 2 (IL-2), heat shock 27 KD protein (hsp27), and CYP19 (aromatase). Induction of p57 Kip2, p53, BRCA2, IL-2, and ATF-2 would be expected to decrease cellular proliferation and increase tumor suppression and/or apoptosis. PEITC treatment produced significant alterations in some genes involved in tumor suppression and cellular proliferation/apoptosis that may be important in explaining the chemopreventive effects of PEITC.

Highlights

Diet and environmental factors may represent very significant factors in the genesis of breast cancer
Induction of apoptosis occurred at low concentrations of Phenethyl isothiocyanate (PEITC) (≤10 μM), and Western blot analyses demonstrated that increased expression of p53 protein was associated with PEITC-induced apoptosis [33]. c-Jun N-terminal kinase (JNK) is involved in PEITC-induced apoptosis, and p53 is known as a substrate of JNK [34]
Recent immunoblot analyses showed that PEITC 3 μM did not increase the protein expression of p53 in MCF-7 cells [35]

Summary

Introduction

Diet and environmental factors may represent very significant factors in the genesis of breast cancer. Organic isothiocyanates (ITCs, R-N=C=S), known as mustard oils, are present in the form of glucosinolates in Brassica and other vegetables of the family Cruciferae (e.g., cabbage, cauliflower, brussels sprouts, watercress, and broccoli, kale) and the genus Raphanus (radishes and daikons) [1]. It has been reported that urinary ITC levels are significantly associated with reduced breast cancer risk in pre- and postmenopausal women [7]. One study demonstrated that Brassica vegetable consumption increases the ratio of 2-hydroxyestrone (a noncarcinogenic metabolite of estrogen) to 16α-hydroxyestrone (a carcinogenic metabolite of estrogen), in healthy postmenopausal women [8]. The mechanisms underlying the chemopreventive effects of ITCs are likely diverse and multifactorial and remain largely unknown at this time

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