Glucosinolates (GL) can inhibit, retard or reverse experimental multistage
carcinogenesis. When brassica plant tissue is broken, GLs are hydrolyzed by the endogenous
enzyme myrosinase (Myr), releasing many products including
isothiocyanates (ITC). Synthetic ITCs like
sulforaphane exert chemopreventive effects against chemically induced
tumors in animals, modulating
enzymes required for
carcinogens' activation/detoxification and/or the induction of cell-cycle arrest and apoptosis in tumor cell lines. To investigate the chemopreventive potential of ITCs while reproducing the circumstances of dietary contact with
sulforaphane, we studied proliferation, apoptosis induction and p53, bcl-2 and
bax protein expression in Jurkat T-
leukemia cells by
sulforaphane, the ITC generated in situ in a quantitative manner by Myr starting from
glucoraphanin (GRA). Jurkat cells were treated with different doses of GRA-Myr mixture. Effects on cell growth or survival were evaluated by counting
trypan blue-excluding cells. Cell-cycle progression, apoptosis and expression of p53, bax and bcl-2
proteins were analyzed by flow cytometry. Results were analyzed by two-sided Fisher's exact test.
Sulforaphane, but not GRA, caused G(2)/M-phase arrest (P = 0.028) and increase of apoptotic cell fraction (P < 0.0001) in a time- and dose-dependent manner.
Necrosis was observed after prolonged exposure to elevated
sulforaphane doses. Moreover, it markedly increased p53 and
bax protein expression, and slightly affected bcl-2 expression. These findings indicate that
sulforaphane but not the native GL GRA can exert both protective and toxic effects inhibiting leukemic cell growth.
Sulforaphane therefore deserves study as a potential chemopreventive/chemotherapeutic antileukemic agent.