Trabajo presentado al FITOMED celebrado en Messina (Italia) en Junio del 2010.- Melchini, Antonietta et al.Peer reviewe

Francisco Candeira, Marta

Melchini, Antonietta

Pasquale, R. de

Traka, Maria

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Promising Selectivity of Dietary Isothiocyanates from CruciferousVegetables for Human Cancer CellsA. Melchiniru'b P. Maimone," M. Francisco,d M. Traka,b R. Mithen,b A. Trovato,c R. DePasquale"oFondqzione "Prof. Antonio Imbesi", Ilniversitd di Messinq, P. zzq Pugliatti l, Messina, Italiq;bPlant NaturalProducts and Health Programme, Institute of Food Reseqrch, Norwích Research Park, Norwich, LlnitedKingdom; "Dipsrtimento Farmaco-Biologico, Facoltd di Fqrmacia, Untuersiñ di Messinq, Vill. Annuwiatd,Messina, Italiq; d Misíón Bíológica de Galicia (CSIC), PO Box 28, Pontevedra, Spain.Consumption of cruciferous vegetables has been associated with a reduced risk indevelopment of various types of cancer [1]. This has been attributed to the bioactivehydrolysis products that are derived from these vegetables, namely isothiocyanates (ITCs) [2].A growing body of evidences from cell and a¡rimal models indicates several molecula¡mechanism of chemoprevention by ITCs, that include moduiation of phase I, II and IIIdetoxification, regulation of cell growth by induction of apoptosis a¡d cell cycle arrest,induction of ROS-mechanisms and regulation androgen receptor pathways [3]. Literature datapresent cunent knowledge on these mecha¡isms of action ofITCs in cancer cell lines to date.However, a primary goal in the anticancer drugs research is the discovery and development offunctional molecules characterized by selective cytotoxicity against cancer cells and lowtoxicity for healthy cells. At present, the effect of ITCs in normal cells has not been fullyinvestigated. The¡e is evidence that the 4-(methylthio) butyl isothiocyanate (erucin, ER) isable to induce a strong antiproliferative effect on human leukemia cells, but not in non-transformed human peripheral T ll,rnphoc¡.'tes [4]. Recently, the selectivity of p-phenylethylisothiocyanate (PEITC) against oncogenically transformed ovarian epithelial cells, includingcisplatin-resistant cells, has been reported [5]. The aim of this study was to evaluate thedifferential response of both normal and cancer cells from human prostate to ER and itsoxidized analog, the 4-(methylsulf,rnyl) butyl isothiocyanate (sulforaphane, SF). The effect ofincreasing concentrations of SF and ER on two different human prostatic cell lines, normalprostate epithelium (PNTIA) and prostate adenocarcinoma cells (PC3) was determinate, andwe went on to provide additional mechanistic information in relation to the potentialselectivity for cancer cells. Our preliminary data demonst¡ate that these structurally relatedITCs exert a specific action on oncogenic signalling pathways, such as p53/p2I andexhacellular signal-regulated kinases (ERK) l/2 pafhways, that could explain the strongerc)'totoxicity observed in cancer cells compared to non malignant cells. Although these dietarybioactive compounds have exhibited selectivity for oncogenically transformed cell lines, ITCselectivity is an area of great interest that warrants further investigation.Riferimenti !l J. V. Higdon, B. Delage, D.E. Williams, R.H. Dashwood Páarmacol Res 2007, 55,224-236; l2lJ. D. Hayes, M.O. Kelleher, I. M. Eggleston E¿r.¡ Nutr 2008.,47,73-88; [3] Y. Nakamura Forum Nutr 2009,61,170-l8l ; [ 4] C. Fimognari, M. Nusse, R. Iori, G. Cantelli-Forti, P. Hrelia Invest New Drugs 2004, 22, ll9-t29;[5] D. Trachootham, Y. Zhou, H. Zhang, Y. Demizu, Z. Chen, H. Pelicano, p.J. Chiao, G. Achanta, R.B.Arlinghaus, J. Liu, P. Ht;,ang Cancer Cell2006,, 10,241-252.

Promising selectivity of dietary isothiocyanates from cruciferous vegetables for human cancer cells

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