In vitro assessment of antiproliferative action selectivity of dietary isothiocyanates for tumor versus normal human cells

Aleksandra Konić Ristić; Tatjana Stanojković; Tatjana Srdić-Rajić; Sanda Dilber; Brižita Đorđević; Ivan Stanković; Zorica Juranić

doi:10.2298/VSP141103066K

Aleksandra Konić Ristić Institute for Medical Research, Centre of Research Excellence in Nutrition and Metabolism, University of Belgrade, Belgrade, Serbia
Tatjana Stanojković Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
Tatjana Srdić-Rajić Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
Sanda Dilber UniveDepartment of Organic Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Brižita Đorđević Department of Bromatology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Ivan Stanković Department of Bromatology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
Zorica Juranić Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia

DOI: https://doi.org/10.2298/VSP141103066K

Ključne reči: isothiocyanates||, ||izotiocijanati, vegetables||, ||povrće, neoplastic cells, circulating||, ||neoplazme, cirkulišuće ćelije, lymphocytes||, ||limfociti, chemoprevention||, ||hemoprevencija,

Sažetak

Uvod/Cilj. Brojne epidemiološke studije pokazale su povoljne efekte konzumiranja povrća iz familije kupusnjača (Brassicaceae) u hemioprevenciji karcinoma. Osnovni biološki aktivni sastojci ovog povrća su izotiocijanati, prisutni u obliku prekursora – glukozinolata. Cilj ovog rada bio je određivanje selektivnosti antiproliferativnog delovanja dijetetskih izotiocijanata na maligne ćelije u odnosu na normalne ćelije. Metode. Antiproliferativna aktivnost tri izotiocijanata zastupljena u ljudskoj ishrani: sulforafana (SFN), benzil-izotiocijanata (BITC) i feniletil-izotiocijanata (FEITC) na humane maligne ćelijske linije, HeLa, ćelijsku liniju karcinoma grlića materice, Fem-x, ćelijsku liniju melanoma, i LS 174, ćelijsku liniju karcinoma kolona, kao i na mononuklearne ćelije periferne krvi (MNĆPK), sa ili bez delovanja mitogena, određivana je MTT kalorimetrijskim testom, 72 h nakon kontinuiranog delovanja agenasa. Rezultati. Svi ispitivani izotiocijanati inhibirali su proliferaciju HeLa, Fem-x i LS 174 ćelija. Na svim ćelijskim linijama BITC je pokazao najizraženije delovanje sa vrednostima polumaksimalne inhibitorne koncentracije (IC₅₀) od 5.04 mmol m^-3 na HeLa ćelijama, 2,76 mmoL m^-3 na Fem-x i 14,30 mmol m^-3 na LS 174 ćelijama. Svi ispitivani izotiocijanati pokazali su citotoksično delovanje na MNĆPK, ali sa višim IC50 vrednostima u odnosu na maligne ćelije. Indeksi selektivnosti antitumorkog delovanja, izraženi kao odnos IC₅₀ vrednosti dobijenih na MNĆPK i malignim ćelijama, bili su između 1,12 i 16,57, sa najvišom vrednosti pri delovanju BITC na Fem-x ćelije. Zaključak. Na osnovu antiproliferativne aktivnosti na maligne ćelije i selektivnosti antiproliferativnog delovanja na maligne u odnosu na normalne ćelije, benzil izotiocijanat se ističe kao perspektivni agens u hemioprevenciji karcinoma. Generalno, pored antitumorskog delovanja, bezbednost primene ovih jedinjenja treba da predstavlja važan kriterijum u izboru odgovarajućih izotiocijanata za primenu u primarnoj, sekundarnoj i tercijarnoj hemioprevenciji kancera. Ispitivanje selektivnosti predstavlja pogodan pristup oceni bezbednosti i prirodnih izotiocijanata i sintetskih analoga.

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In vitro ispitivanje selektivnosti antiproliferativnog dejstva dijetetskih izotiocijanata na tumorske u odnosu na normalne humane ćelije

Sažetak

Reference