Title

 

Authors

A. Melchini^1,2, P. Maimone¹, N. Miceli¹, M.F. Taviano¹, S. Catania³, A. Trovato¹, R. De Pasquale¹ and C. Costa^3
 
1Pharmaco-Biological Dept., School of Pharmacy, University of Messina, 98168 Messina, Italy
²Plant Natural Products and Health Dept., Institute of Food Research, Norwich Research Park, NR47LX Norwich, United Kingdom
³Interdepartmental Centre of Experimental, Environmental and Occupational Toxicology (CITSAL), University of Messina, 98125 Messina, Italy 

 

Abstract

At present, experimental data can lead to candidate the dietary compound erucin (4-(methylthio) butyl isothiocyanate, ER) as a new promising anticarcinogenic phytochemical (Melchini and Traka, 2010). The isothiocyanate ER is obtained from enzymatic hydrolysis of glucoerucin, isolated for the first time in the 1970s from seeds of Eruca sativa Mill. and overall found at high levels in rocket salad species, but also through in vivo reduction of the isothiocyanate sulforaphane (SF), that structurally represents its oxidized analog, characteristic of broccoli (Brassica oleracea L. ssp. italica) (Gmelin et al., 1970; Kassahun et al., 1997). Recent studies have highlighted the differential effects on cell proliferation exerted by dietary isothiocyanates (ITCs) in normal and cancerous cells (Clarke et al., 2011; Zeng et al., 2011; Powolny et al., 2010; Telang et al., 2009). The in vitro study carried out by Fimognari and colleagues has provided the only evidence that ER is able to induce a strong antiproliferative effect on human leukaemia cells, but not in non-transformed human peripheral T lymphocytes (Fimognari et al., 2004). However, the potential selectivity of ER against cancer cells not affecting normal cell growth has not been shown in other cell lines. The aim of this study was to evaluate the effects of ER on the proliferation of non cancerous lung cells comparing data already obtained on human lung cancer A549 cells (Melchini et al., 2009). To help to elucidate whether the effects of ER are potentially selective in lung cancer cells, the effects of ER on cell viability and processes involved on the physiological control of cell growth have been studied in vitro using normal bronchial epithelial (BEAS) cells. Our data showed that ER did not affect the viability of BEAS cells at concentrations that may be achievable in humans (1-2 µM) after consumption of cruciferous vegetables. Moreover, the expression of the cyclin-dependent kinase (CDKs) inhibitor p21^WAF1/CIP1 (p21) and p53 proteins in BEAS cells has not been changed by ER concentrations as high as 25 µM. Contrary previous data reported that ER affects the proliferation of lung cancer A549 cells enhancing significantly p21 and p53 protein expression in a dose-dependent manner (p < 0.001) (Melchini et al., 2009). Comparison of data using normal lung BEAS cells with those obtained with lung cancer A549 cells underlines the potential selectivity of ER against cancer cells. It is clearly important that further studies need to be performed in order to understand the specific action of ER and other ITCs on oncogenic signalling pathways to extend the potential selectivity of dietary ITCs as a significant therapeutic application.
 
Clarke et al. (2011). Mol Nutr Food Res. in press.
Finognari et al. (2004). Invest. New Drugs. 22, 119-29.
Gmelin et al. (1970). Arch Pharm Ber Dtsch Pharm Ges. 303, 330–34.
Kassahun et al (1997). Chem Res Toxicol. 10, 1228–33.
Melchini and Traka (2010). Toxins. 2, 593-612.
Melchini et al. (2009). Food Chem Tox. 47, 1430–36.
Powolny et al. (2010). Pharm Res. 27, 2766-75.
Telang et al. (2009). Exp Biol Med. 234, 287-95.
Zeng et al. (2011). Nutr Cancer.63, 248-55.