ABSTRACT
Title
Biological profile of the 4-(methylthio) butyl isothiocyanate: a new promising anticancer agent from cruciferous vegetables
Authors
A. Melchini1, 2
1Dept. of Plant Natural Products and Health, Institute of Food Research, Norwich, United Kingdom
2Dept. of Pharmaco-Biology, School of Pharmacy, University of Messina, Messina, Italy
1Dept. of Plant Natural Products and Health, Institute of Food Research, Norwich, United Kingdom
2Dept. of Pharmaco-Biology, School of Pharmacy, University of Messina, Messina, Italy
Abstract
Brassica, or cruciferous, vegetables are commonly included in human diet and are highly recommended for their nutritional value and health-promoting effects [1]. The protective effects of cruciferous vegetables consumption against chronic diseases appears to be mainly related to the activity of isothiocyanates (ITCs), bioactive hydrolysis products that are derived from these vegetables [2]. Consumption of cruciferous vegetables has been mainly associated with a reduced risk in the development of various types of cancer [3]. A growing body of evidences from cell and animal models indicates several molecular mechanism of chemoprevention by ITCs that include modulation of phase I, II and III detoxification, regulation of cell growth by induction of apoptosis and cell cycle arrest, induction of ROS-mechanisms and regulation androgen receptor pathways [4]. Although a lot of research has focused mainly on sulforaphane (SF), derived from broccoli, and phenyl ethyl ITC (PEITC), derived from watercress, other ITCs such as the 4-(methylthio) butyl ITC (erucin, ER) are promising [5]. 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 (Eruca ssp. Mill, Diplotaxis ssp. L.)[6]. Experimental evidences, obtained in rats and humans, have shown the formation of ER also through in vivo reduction of the isothiocyanate SF, that structurally represents its oxidized analogue, characteristic of broccoli (Brassica oleracea L. ssp. italica) [7, 8]. The dietary isothiocyanate ER has demonstrated promising anticancer effects in various in vitro and in vivo studies [5] and can be considered a naturally occurring ITC able to affect selectively cancer cell growth [9]. However, there are few evidences of its effects on human non cancerous cells to date. In the current study, the biological activity of ER was investigated on normal and cancer cells by analysing molecular pathways which play an important role in restraining mammalian cell growth by cytostatic and apoptotic actions under physiological conditions. It is clearly important for the translation of laboratory findings to clinical approaches to understand the molecular mechanisms by which phytochemicals may exert health promoting effects.
[1] Verkerk et al. (2009) Glucosinolates in Brassica vegetables: the influence of the food supply chain on intake, bioavailability and human health. Mol Nutr Food Res 53, S219.
[2] Kris-Etherton et al. (2002) Bioactive compounds in foods: Their role in the prevention of cardiovascular disease and cancer. American Journal of Medicine 113, 71S-88S.
[3] Hecht (2000) Inhibition of carcinogenesis by isothiocyanates. Drug Metab Rev 32, 395-411.
[4] Nakamura (2009) Chemoprevention by isothiocyanates: molecular basis of apoptosis induction. Forum Nutr 61, 170-81.
[5] Melchini and Traka (2010) Biological profile of erucin: a new promising anticancer agent from cruciferous vegetables. Toxins 2,593-612.
[6] Gmelin and Schluter (1970) Isolation of 4-methylthiobutylglucosinolate (glucoerucin) from seeds of Eruca sativa Mill. Arch Pharm Ber Dtsch Pharm Ges 303, 330-4.
[7] Kassahun et al. (1997) Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat: identification of phase I metabolites and glutathione conjugates. Chem Res Toxicol 10, 1228-33.
[8] Vermeulen et al. (2006) Association between consumption of cruciferous vegetables and condiments and excretion in urine of isothiocyanate mercapturic acids. J Agric Food Chem 54, 5350-8.
[9] Fimognari et al. (2004) The new isothiocyanate 4-(methylthio)butylisothiocyanate selectively affects cell-cycle progression and apoptosis induction of human leukemia cells. Investigational New Drugs 22, 119-129.
[1] Verkerk et al. (2009) Glucosinolates in Brassica vegetables: the influence of the food supply chain on intake, bioavailability and human health. Mol Nutr Food Res 53, S219.
[2] Kris-Etherton et al. (2002) Bioactive compounds in foods: Their role in the prevention of cardiovascular disease and cancer. American Journal of Medicine 113, 71S-88S.
[3] Hecht (2000) Inhibition of carcinogenesis by isothiocyanates. Drug Metab Rev 32, 395-411.
[4] Nakamura (2009) Chemoprevention by isothiocyanates: molecular basis of apoptosis induction. Forum Nutr 61, 170-81.
[5] Melchini and Traka (2010) Biological profile of erucin: a new promising anticancer agent from cruciferous vegetables. Toxins 2,593-612.
[6] Gmelin and Schluter (1970) Isolation of 4-methylthiobutylglucosinolate (glucoerucin) from seeds of Eruca sativa Mill. Arch Pharm Ber Dtsch Pharm Ges 303, 330-4.
[7] Kassahun et al. (1997) Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat: identification of phase I metabolites and glutathione conjugates. Chem Res Toxicol 10, 1228-33.
[8] Vermeulen et al. (2006) Association between consumption of cruciferous vegetables and condiments and excretion in urine of isothiocyanate mercapturic acids. J Agric Food Chem 54, 5350-8.
[9] Fimognari et al. (2004) The new isothiocyanate 4-(methylthio)butylisothiocyanate selectively affects cell-cycle progression and apoptosis induction of human leukemia cells. Investigational New Drugs 22, 119-129.